Gann Ting - Academia.edu (original) (raw)
Papers by Gann Ting
Nuclear Medicine Communications, May 1, 1998
ABSTRACT Radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis... more ABSTRACT Radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radiopharmaceuticals from the treated joints. Leakage can be minimized by selecting particles of an appropriate size. In this study, we labelled microspheres with Re-188 and analysed its biodistribution after intra-articular injection in rabbits with antigen-induced arthritis. Gamma camera imaging was performed to quantify the mean retention of Re-188 in the knees. The mean retention of Re-188 was 98.7, 94.6 and 93.6% at 1, 24 and 48 h, respectively. The biodistribution data revealed very low radioactivity in all organs at different times, which suggests the leakage of radiotracer from the knee was negligible. Our preliminary results indicate that Re-188 microspheres are a potentially effective radiopharmaceutical for radiation synovectomy. ((C) 1998 Lippincott-Raven Publishers).
Applied Radiation and Isotopes, 1996
We have evaluated several factors in an attempt to minimize the reduced yields observed after “we... more We have evaluated several factors in an attempt to minimize the reduced yields observed after “wet” storage of 188W/188Re generators, which include the dispersion of 188W-tungstic acid in the alumina column bed by pre-mixing with silica gel, incorporation of cupric ion as an antioxidant in the adsorbent, and elution of the alumina columns with saline solution containing ascorbic acid. The
PubMed, Feb 1, 2003
Background: Patients who receive percutaneous transluminal coronary angioplasty (PTCA) are often ... more Background: Patients who receive percutaneous transluminal coronary angioplasty (PTCA) are often haunted by restenosis of the target vessel within 6 months. Intracoronary irradiation has been shown to alter the luminal narrowing response after balloon angioplasty. Methods: The Taiwan Radiation in Prevention of Post-Pure Balloon Angioplasty Restenosis-I (TRIPPER-I) study evaluated the feasibility, safety, and 6-month angiographic restenosis with intracoronary irradiation after pure balloon angioplasty (POBA) of de novo and post-POBA restenotic lesions in native coronary arteries using a self-centering beta-emitter rhenium-188 (Re-188)-filled balloon. Results: Forty patients received 14 Gy at a 0.5-mm tissue depth with a Re-188 solution-filled perfusion balloon catheter, and 25 control patients received 5-min inflation with a perfusion balloon catheter. There were no procedural complications or in-hospital or 30-day major adverse cardiac events. Six-month angiographic follow-up was performed on 39 Re-188 (97.5%) and 25 control patients (100%). The restenosis rate was 49% in the Re-188 and 56% in the control groups (p=0.62). The composite end-points of death, myocardial infarction, and target-vessel revascularization were 40% in the Re-188 group and 36% in the control group (p=0.80). Conclusions: Catheter-based radiotherapy after POBA of de novo and post-POBA restenotic lesions with a Re-188-filled balloon is feasible but was ineffective in reducing target lesion restenosis with a dose of 14 Gy delivered at a 0.5-mm tissue depth in this study.
PubMed, Oct 1, 1998
Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary... more Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary liver tumor. However, complicated preparation and lack of a gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re, a generator-produced radioisotope with 155-keV gamma ray emission, to label microspheres. After intratumoral injection of 188Re microspheres into rats with hepatoma, biodistributions and survival times were analyzed. Methods: Twelve male rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point) after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations. In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats in each group) to evaluate survival time. Group 1 received intratumoral injection of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and received an intratumoral injection of 0.1 ml normal saline only. Survival time was calculated from the day of injection to 2 mo after treatment. Results: Radioactivity in the tumor was very high throughout. Biological half-time was 170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but declined rapidly over time. The concentration in the urine was approximately 6.14% i.d./ml after the first hour and rapidly declined thereafter. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis and whole blood, were quite low throughout the study. Twelve of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after injection of normal saline only. The difference between the groups was significant (p < 0.05). Conclusion: Rhenium-188 offers cost-effectiveness, on-site availability, short half-life, energetic beta particle, emission of gamma photons for imaging, easy preparation, easy clinical administration and apparent lack of radiation leakage from the treated tumor. Direct intratumoral injection of 188Re microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.
PubMed, Feb 1, 2004
Functional brain imaging targeting the presynaptic dopamine nerve terminal of the nigrostriatal s... more Functional brain imaging targeting the presynaptic dopamine nerve terminal of the nigrostriatal system has been used for monitoring disease progression and evaluating therapeutic effectiveness in patients with Parkinson's disease (PD). (99m)Tc-TRODAT-1 binds with high selectivity to the dopamine transporters in the striatum and can be imaged with SPECT 4 h after injection. We studied the test and retest reproducibility of (99m)Tc-TRODAT-1 SPECT measures in patients with PD to assess the reliability of (99m)Tc-TRODAT-1 for longitudinal evaluation of the nigrostriatal dopaminergic function. Methods: Each of 20 patients with PD underwent 2 (99m)Tc-TRODAT-1 SPECT scans at an interval of 2-3 wk. Patients were imaged 4 h after injection of 925 MBq (99m)Tc-TRODAT-1. Two imaging outcome measures were evaluated: the ratio of specific-striatal-to-nonspecific uptake and the striatal asymmetry index. For both measures, the test/retest variability was calculated. Reproducibility of the 2 outcome measures was evaluated in terms of intraclass correlation coefficient (ICC) and 95% limits of agreement. Results: The mean ratio of specific-striatal-to-nonspecific uptake showed excellent test/retest reproducibility with a mean variability of 10.20%, an ICC of 0.95 (95% confidence interval = 0.88-0.98), and 95% limits of agreement, ranging from -0.19 to 0.19. The striatal asymmetry index had larger test/retest variability (60.41%), a slightly smaller ICC of 0.86 (95% confidence interval = 0.65-0.95), and a wider range of 95% limits of agreement (-16.09 to 15.19). In addition, there was a significant negative correlation between the mean ratio of specific-striatal-to-nonspecific uptake and the motor subscore of the Unified Parkinson's Disease Rating Scale in both test and retest conditions. Conclusion: Our data indicate that the imaging outcome expressed by the mean ratio of specific-striatal-to-nonspecific uptake has an excellent test/retest reproducibility and correlates with disease severity. These findings suggest that (99m)Tc-TRODAT-1 SPECT imaging is useful and feasible for measuring disease progression in PD.
PubMed, Oct 1, 2009
Cancer is the second leading cause of death in the world. Radiolabeled nanocarriers or nanopartic... more Cancer is the second leading cause of death in the world. Radiolabeled nanocarriers or nanoparticles can be designed and used for cancer diagnostic and therapeutic purposes when tagged with appropriate radionuclides. Current progress in nanotechnology and nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers able to deliver radionuclide payloads in a selective manner to improve the efficacy and safety of cancer imaging and therapy. The major nanocarriers include liposomes, dendrimers, quantum dots, iron oxide and carbon nanotubes. In addition, the combining of tumor specific multifunctional and multimodality nanocarriers will hopefully achieve earlier tumor detection and better tumor treatment. Several radiolabeled multifunctional and multimodality nanoparticles have been effectively demonstrated in detecting and treating cancer in animal models. However, further preclinical and clinical efficacy and toxicity studies are required to translate these advanced technologies to the health care of cancer patients. The aim of this article is to provide a brief overview of current status of applications, advantages and up-to-date research and development of nanotargeted radiopharmaceuticals in cancer imaging and therapy.
Nuclear Medicine and Biology, Nov 1, 1999
In the past, many diphosphonates were introduced as bone scan radiopharmaceuticals. In addition, ... more In the past, many diphosphonates were introduced as bone scan radiopharmaceuticals. In addition, diphosphonates have been labeled with beta-emitted isotopes and developed into useful therapeutic drugs for bone metastases. However, it is not clear which diphosphonate is the best choice when labeling with Re-188. In this study, we labeled methylene diphosphonate (MDP), hydroxyethylidene diphosphonate (HEDP), and hydroxymethane diphosphonate (HDP) with Re-188. Each radiopharmaceutical was further evaluated in two conditions (with and without carrier). Twenty-four rabbits were used (four in each group) for the analysis of the biodistributions and bone uptakes of these radiopharmaceuticals to assess their potential for clinical applicability. Four hours after intravenous injection of approximately 37 MBq (1 mCi) Re-188-labeled diphosphonate preparations, whole body scans were performed using a large-field gamma camera equipped with a high resolution collimator. Bone-to-soft tissue ratios (B/S ratio) were calculated using a computer program. Our data showed that Re-188 HEDP with carrier (10(-4) M carrier) could accumulate in the skeletal system whereas very little absorption by bone was observed in the rabbits that were injected with carrier-free Re-188 HEDP. In addition, no significant bone uptake was demonstrated for Re-188 MDP or Re-188 HDP, with or without carrier. The B/S ratio was 25.06 in the Re-188 HEDP with carrier group but less than 3 in the other groups. In conclusion, HEDP is the best choice among these three bone-seeking drugs when labeled with Re-188. But, it is necessary to add carrier when preparing Re-188 HEDP for the treatment of bone metastases.
Nuclear Medicine and Biology, May 1, 1999
Rhenium-186 (Re-186) hydroxyethylidene diphosphonate (HEDP) has been shown to localize in metasta... more Rhenium-186 (Re-186) hydroxyethylidene diphosphonate (HEDP) has been shown to localize in metastatic foci within bone in a manner similar to Tc-99m bone-seeking agents. Usually, in the preparation of diagnostic Tc-99m radiopharmaceuticals, the concentration of Tc is at trace level (10(-8) M). However, large amounts of carrier are included in the preparation of Re-186 radiopharmaceuticals (10(-4) M), which may significantly affect the preparation of Re-HEDP. In this study, Re-188 was used as an Re tracer. The effects of pH and concentrations of Re carrier on the preparation of Re-HEDP were investigated. Re-188-Sn-HEDP was prepared by reconstitution of a kit of lyophilized HEDP mixture, and tin chloride with a radioactive solution of perrhenate in saline. The total concentration of Re present in this work ranged from 10(-8) to 10(-3) M. The results showed that high labeling efficiency was obtained for each preparation. Although the chemical behaviors of the Re-188 HEDP complexes, with and without carrier, were similar, the biodistribution patterns of carrier free Re-188 HEDP in rats were found to differ from the biodistribution patterns of carrier-added Re-188 HEDP.
PubMed, Mar 1, 2001
The aim of this study was to use brain SPECT to differentiate vascular parkinsonism (VP) from Par... more The aim of this study was to use brain SPECT to differentiate vascular parkinsonism (VP) from Parkinson's disease. Methods: Fourteen VP patients (age range, 59-87 y; mean age, 70 +/- 7.5 y), 30 Parkinson's disease patients (age range, 54-84 y; mean age, 65 +/- 8.8 y), and 26 healthy (control) individuals (age range, 50-85 y; mean age, 60 +/- 9 y) were examined. A 925-MBq (25 mCi) dose of (99m)Tc-TRODAT-1 was injected intravenously, and brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific striatal (99m)Tc-TRODAT-1 binding was measured and compared. Results: After a region-of-interest analysis of the images from VP patients, Parkinson's disease patients, and healthy volunteers was performed to obtain ratios of putamen to occipital and striatal to occipital binding as a measurement of specific binding to the dopamine transporters in these regions of the brain, where dopamine neurons are concentrated, the specific binding in the 14 VP patients was slightly lower than but not statistically different from that of the healthy individuals in both putamen and caudate areas. A significant decrease in uptake of (99m)Tc-TRODAT-1 in the striatum (P<0.01) was found in Parkinson's disease patients. Reduction of the uptake was more pronounced in the contralateral putamen of Parkinson's disease patients than that of VP patients (P<0.001). A significant bilateral striatal asymmetry was also observed in Parkinson's disease patients but not in VP patients (P< 0.01). Conclusion: Our findings clearly show that, for VP patients, (99m)Tc-TRODAT-1 SPECT is a reliable method to differentiate VP from Parkinson's disease. Further studies, including those to differentiate Parkinson's disease from arteriosclerotic parkinsonism and patients with both VP and Parkinson's disease, are needed to help rule out the possibility of Parkinson's disease as early as possible.
Applied Radiation and Isotopes, Dec 1, 1993
The separation of carrier-free 9oy from fission product WSr by solid supported solvent extraction... more The separation of carrier-free 9oy from fission product WSr by solid supported solvent extraction chromatography was investigated using Teflon grain as solid support and a di-(Zethylhexyl) phosphoric acid (D2EHPA) extraction agent as liquid phase. The optimum separation conditions are: (1) solid support using Dupont TFSOO Tetlon grains, (2) using 5% DZEHPA extraction agent as liquid phase, (3) setting the flow rate at 1 &/mm. and (4) using a column diameter of 0.5 cm which was packed with 1 g treated Teflon. After loading ?Sr/9oy equilibrium solution, the loaded column was washed with 0.3 N hydrochloric acid to remove ?Sr species; subsequently, 8 N hydrochloric acid was used as an eluent to obtain a 9oy solution. Chemical yield was about 90%; radionuclide impurity of ?Sr in the final product was < 10e6%. Consequently, the preparation of 1 mCi of 9oy was satisfactory for radiolabeling in medical applications. A radiotracer method using 05Sr and ssY was also developed to investigate separation efficiency.
![Research paper thumbnail of In vivo quantification by SPECT of [123I] ADAM bound to serotonin transporters in the brains of rabbits](https://attachments.academia-assets.com/109144492/thumbnails/1.jpg)
](Nuclear Medicine and Biology, Nov 1, 2004
Background: A novel radioiodine ligand [ 123 I] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5... more Background: A novel radioiodine ligand [ 123 I] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) has been suggested as a promising serotonin transporter (SERT) imaging agent for the central nervous system. In this study, the biodistribution of SERTs in the rabbit brain was investigated using [ 123 I] ADAM and mapping images of the same animal produced by both single-photon emission computed tomography (SPECT) and microautoradiography. A semiquantification method was adopted to deduce the optimum time for SPECT imaging, whereas the input for a simple fully quantitative tracer kinetic model was provided from arterial blood sampling data. Methods: SPECT imaging was performed on female rabbits postinjection of 185 MBq [ 123 I] ADAM. The time-activity curve obtained from the SPECT images was used to quantify the SERTs, for which the binding potential was calculated from the kinetic modeling of [ 123 I] ADAM. The kinetic data were analyzed by the nonlinear least squares method. The effects of the selective serotonin reuptake inhibitors fluoxetine and p-chloroamphetamine (PCA) on rabbits were also evaluated. After scanning, the same animal was sacrificed and the brain was removed for microautoradiography. Regions-of-interest were analyzed using both SPECT and microautoradiography images. The SPECT images were coregistered manually with the corresponding microautoradiography images for comparative study. Results: During the time interval 90-100 min postinjection, the peak specific binding levels in different brain regions were compared and the brain stem was shown to have the highest activity. The target-to-background ratio was 1.89F0.02. Similar studies with fluoxetine and PCA showed a background level for SERT occupation. Microautoradiography demonstrated a higher level of anatomical details of the [ 123 I] ADAM distribution than that obtained by SPECT imaging of the rabbit brain. Conclusion: SPECT imaging of the rabbit brain with [ 123 I] ADAM showed high affinity, high specificity, and favorable kinetics. The timeactivity curve showed that the accumulation of the [ 123 I] ADAM in the brain stem reached a maximum between 90 and 100 min postinjection. The microautoradiography provides high-resolution images of the rabbit brain. Our results for the [ 123 I] ADAM biodistribution in the rabbit brains demonstrate that this new radioligand is suitable as a selective SPECT imaging agent for SERTs.
Journal of Radioanalytical and Nuclear Chemistry, Sep 1, 1999
The evaluation of the pharmacokinetics of pure, beta radiopharmaceuticals is not possible with sc... more The evaluation of the pharmacokinetics of pure, beta radiopharmaceuticals is not possible with scintigraphy. Both whole-body autoradiography (WBAR) and Packard Instantimager, a device for rapid imaging, were used to study the whole body distribution of 7-and I~-emitting radionuclides (99mTc-MDP, 99mTc-sulftlr colloid, or ISSRe-HEDP), and results obtained from both methods were compared. The biodistribution of 99mTc-MDP and ISSRe-HEDP were seen mainly in bones including skull, spine, and vertebrae of spine and cardiac and skeletal muscles. The 99mTc-sulfur colloid localized in liver, bone marrow, and spleen. The resolution of WBAR is superior than that of Packard Instantimager. However, the advantage of Packard Instantimager is that rapid imaging within few minutes is possible with it, while WBAR imaging requires several hours to days.
Nuclear Medicine and Biology, Oct 1, 2001
In this study, the effectiveness of a 188 Re labeled sulfur colloid with two particle size ranges... more In this study, the effectiveness of a 188 Re labeled sulfur colloid with two particle size ranges was used to evalucate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. Methods: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10melanoma-bearing BDF 1 mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x10 5 B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (nϭ16ϳ18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes (Ͻ3m:80.4 Ϯ7.2%, colloid 1) and the other receiving larger particle sizes (Ͻ3m:12.3Ϯ1.0%, colloid 2). The animals were checked daily until death and their survival recorded. Results: Colloid 2 showed higher accumulation in almost all tissues, the highest accumulation organ was tumor (ϳ 40%), then spleen (ϳ20%), stomach (ϳ15%), diaphragm (ϳ3%), and liver (ϳ2%). There was a significant increase in survival time with increasing amount of the larger-particle-size colloid. Administered levels of 16-31 MBq/mouse were most efficacious and with higher amounts the survival times decreased significantly below that of the controls. There was a significant difference in the dose-response curves for the two preparations. Protection factors (1/Relative-risk) of nearly 5 were achieved using the larger colloid size, and nearly 30 using the smaller colloid size. An amount of 16-31 MBq of the colloid 2 was the optimal activity in these studies. On the one hand, the survival data agreed well with the biodistribution data, where higher accumulation was found in tumor with colloid 2. Conclusion: Rhenium-188 offers on-site availability, medium half-life, higher beta-particle energy of 2.12 MeV for therapy and emission of 155keV gamma photon suitable for imaging. The present study demonstrated that 188 Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals.
Applied Radiation and Isotopes, Mar 1, 1996
In this study we prepared and analyzed the biodistribution of 188Re-labelled Lipiodol ([188-Re]-L... more In this study we prepared and analyzed the biodistribution of 188Re-labelled Lipiodol ([188-Re]-Lipiodol) in rats after intrahepatic arterial injection. EDTB was synthesized by condensation of 1,2-benzenediamine and ethylenediaminetetraacetic acid (EDTA). The labelling efficiency of [188Re] Lipiodol was determined to be greater than 97% by ITLC developed with n-hexane. Following incubation of the [188Re] Lipiodol with an equal volume of serum
Nuclear Medicine and Biology, Nov 1, 1999
Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However... more Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However, its clinical value is reduced by a high restenosis rate. A new concept in preventing restenosis is the use of a liquid-filled balloon containing a beta-emitting radioisotope. In this study, we performed biodistribution studies of Re-188 perrhenate and Re-188 diethylenetriaminopentaacetate (DTPA) to assess the resulting organ dose values in the event of balloon rupture if these agents are used for the clinical inhibition of restenosis after percutaneous transluminal coronary angioplasty (PTCA). After injecting Re-188 preparations intravenously, rats were killed at 10 min, 30 min, 60 min, 2 h, and 6 h (n ؍ 5 per group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (%ID/g or %ID/mL). In addition, urine excretion and thyroid gland uptake were evaluated in rats (n ؍ 5 per group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed that both agents were excreted primarily via urine. However, the excretion of Re-188 DTPA was much faster than that of Re-188 perrhenate via the urinary system. The biodistribution data revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA group. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for both agents. The thyroid radiation value in the Re-188 perrhenate group was 0.163 mGy/MBq, which was much higher than that of the Re-188 DTPA group (0.0167 mGy/MBq). The stomach radiation value was as high as 0.127 mGy/MBq for Re-188 perrhenate, compared with 0.013 mGy/MBq for Re-188 DTPA. In conclusion, in the event of balloon rupture, the release of Re-188 DTPA results in lower radiation doses than Re-188 perrhenate, especially to the thyroid gland and the stomach. Our data suggest that Re-188 DTPA is a useful radiopharmaceutical for endovascular irradiation.
The Journal of Nuclear Medicine, May 1, 2011
International Journal of Molecular Sciences, Apr 8, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Radioanalytical and Nuclear Chemistry, Oct 1, 1998
ABSTRACT In recent years chances of using rhenium-186 and rhenium-188 as radioactive isotopes in ... more ABSTRACT In recent years chances of using rhenium-186 and rhenium-188 as radioactive isotopes in diagnostic and therapeutic applications are increased very much due to the characteristic radiochemical and chemical properties of these two radioisotopes. In particular, chemical similarities between99Tc and99mTc pair and186Re and188Re pair make it easier to correlate the two groups of compounds. Rhenium-188 is generated from the beta-decay of tungsten-188 which was produced by double neutron capture on enriched tungsten-186 oxide. It is of great interest to examine the impurities in the eluate by radiochemical neutron activation. For this purpose, the preconcentration of the impurities in samples were necessary, and it was achieved by adsorption on hydrated magnesium oxide.
Nuclear Medicine Communications, May 1, 1998
ABSTRACT Radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis... more ABSTRACT Radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radiopharmaceuticals from the treated joints. Leakage can be minimized by selecting particles of an appropriate size. In this study, we labelled microspheres with Re-188 and analysed its biodistribution after intra-articular injection in rabbits with antigen-induced arthritis. Gamma camera imaging was performed to quantify the mean retention of Re-188 in the knees. The mean retention of Re-188 was 98.7, 94.6 and 93.6% at 1, 24 and 48 h, respectively. The biodistribution data revealed very low radioactivity in all organs at different times, which suggests the leakage of radiotracer from the knee was negligible. Our preliminary results indicate that Re-188 microspheres are a potentially effective radiopharmaceutical for radiation synovectomy. ((C) 1998 Lippincott-Raven Publishers).
Applied Radiation and Isotopes, 1996
We have evaluated several factors in an attempt to minimize the reduced yields observed after “we... more We have evaluated several factors in an attempt to minimize the reduced yields observed after “wet” storage of 188W/188Re generators, which include the dispersion of 188W-tungstic acid in the alumina column bed by pre-mixing with silica gel, incorporation of cupric ion as an antioxidant in the adsorbent, and elution of the alumina columns with saline solution containing ascorbic acid. The
PubMed, Feb 1, 2003
Background: Patients who receive percutaneous transluminal coronary angioplasty (PTCA) are often ... more Background: Patients who receive percutaneous transluminal coronary angioplasty (PTCA) are often haunted by restenosis of the target vessel within 6 months. Intracoronary irradiation has been shown to alter the luminal narrowing response after balloon angioplasty. Methods: The Taiwan Radiation in Prevention of Post-Pure Balloon Angioplasty Restenosis-I (TRIPPER-I) study evaluated the feasibility, safety, and 6-month angiographic restenosis with intracoronary irradiation after pure balloon angioplasty (POBA) of de novo and post-POBA restenotic lesions in native coronary arteries using a self-centering beta-emitter rhenium-188 (Re-188)-filled balloon. Results: Forty patients received 14 Gy at a 0.5-mm tissue depth with a Re-188 solution-filled perfusion balloon catheter, and 25 control patients received 5-min inflation with a perfusion balloon catheter. There were no procedural complications or in-hospital or 30-day major adverse cardiac events. Six-month angiographic follow-up was performed on 39 Re-188 (97.5%) and 25 control patients (100%). The restenosis rate was 49% in the Re-188 and 56% in the control groups (p=0.62). The composite end-points of death, myocardial infarction, and target-vessel revascularization were 40% in the Re-188 group and 36% in the control group (p=0.80). Conclusions: Catheter-based radiotherapy after POBA of de novo and post-POBA restenotic lesions with a Re-188-filled balloon is feasible but was ineffective in reducing target lesion restenosis with a dose of 14 Gy delivered at a 0.5-mm tissue depth in this study.
PubMed, Oct 1, 1998
Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary... more Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary liver tumor. However, complicated preparation and lack of a gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re, a generator-produced radioisotope with 155-keV gamma ray emission, to label microspheres. After intratumoral injection of 188Re microspheres into rats with hepatoma, biodistributions and survival times were analyzed. Methods: Twelve male rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point) after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations. In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats in each group) to evaluate survival time. Group 1 received intratumoral injection of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and received an intratumoral injection of 0.1 ml normal saline only. Survival time was calculated from the day of injection to 2 mo after treatment. Results: Radioactivity in the tumor was very high throughout. Biological half-time was 170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but declined rapidly over time. The concentration in the urine was approximately 6.14% i.d./ml after the first hour and rapidly declined thereafter. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis and whole blood, were quite low throughout the study. Twelve of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after injection of normal saline only. The difference between the groups was significant (p < 0.05). Conclusion: Rhenium-188 offers cost-effectiveness, on-site availability, short half-life, energetic beta particle, emission of gamma photons for imaging, easy preparation, easy clinical administration and apparent lack of radiation leakage from the treated tumor. Direct intratumoral injection of 188Re microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.
PubMed, Feb 1, 2004
Functional brain imaging targeting the presynaptic dopamine nerve terminal of the nigrostriatal s... more Functional brain imaging targeting the presynaptic dopamine nerve terminal of the nigrostriatal system has been used for monitoring disease progression and evaluating therapeutic effectiveness in patients with Parkinson's disease (PD). (99m)Tc-TRODAT-1 binds with high selectivity to the dopamine transporters in the striatum and can be imaged with SPECT 4 h after injection. We studied the test and retest reproducibility of (99m)Tc-TRODAT-1 SPECT measures in patients with PD to assess the reliability of (99m)Tc-TRODAT-1 for longitudinal evaluation of the nigrostriatal dopaminergic function. Methods: Each of 20 patients with PD underwent 2 (99m)Tc-TRODAT-1 SPECT scans at an interval of 2-3 wk. Patients were imaged 4 h after injection of 925 MBq (99m)Tc-TRODAT-1. Two imaging outcome measures were evaluated: the ratio of specific-striatal-to-nonspecific uptake and the striatal asymmetry index. For both measures, the test/retest variability was calculated. Reproducibility of the 2 outcome measures was evaluated in terms of intraclass correlation coefficient (ICC) and 95% limits of agreement. Results: The mean ratio of specific-striatal-to-nonspecific uptake showed excellent test/retest reproducibility with a mean variability of 10.20%, an ICC of 0.95 (95% confidence interval = 0.88-0.98), and 95% limits of agreement, ranging from -0.19 to 0.19. The striatal asymmetry index had larger test/retest variability (60.41%), a slightly smaller ICC of 0.86 (95% confidence interval = 0.65-0.95), and a wider range of 95% limits of agreement (-16.09 to 15.19). In addition, there was a significant negative correlation between the mean ratio of specific-striatal-to-nonspecific uptake and the motor subscore of the Unified Parkinson's Disease Rating Scale in both test and retest conditions. Conclusion: Our data indicate that the imaging outcome expressed by the mean ratio of specific-striatal-to-nonspecific uptake has an excellent test/retest reproducibility and correlates with disease severity. These findings suggest that (99m)Tc-TRODAT-1 SPECT imaging is useful and feasible for measuring disease progression in PD.
PubMed, Oct 1, 2009
Cancer is the second leading cause of death in the world. Radiolabeled nanocarriers or nanopartic... more Cancer is the second leading cause of death in the world. Radiolabeled nanocarriers or nanoparticles can be designed and used for cancer diagnostic and therapeutic purposes when tagged with appropriate radionuclides. Current progress in nanotechnology and nanomedicine has exploited the possibility of designing tumor-targeted nanocarriers able to deliver radionuclide payloads in a selective manner to improve the efficacy and safety of cancer imaging and therapy. The major nanocarriers include liposomes, dendrimers, quantum dots, iron oxide and carbon nanotubes. In addition, the combining of tumor specific multifunctional and multimodality nanocarriers will hopefully achieve earlier tumor detection and better tumor treatment. Several radiolabeled multifunctional and multimodality nanoparticles have been effectively demonstrated in detecting and treating cancer in animal models. However, further preclinical and clinical efficacy and toxicity studies are required to translate these advanced technologies to the health care of cancer patients. The aim of this article is to provide a brief overview of current status of applications, advantages and up-to-date research and development of nanotargeted radiopharmaceuticals in cancer imaging and therapy.
Nuclear Medicine and Biology, Nov 1, 1999
In the past, many diphosphonates were introduced as bone scan radiopharmaceuticals. In addition, ... more In the past, many diphosphonates were introduced as bone scan radiopharmaceuticals. In addition, diphosphonates have been labeled with beta-emitted isotopes and developed into useful therapeutic drugs for bone metastases. However, it is not clear which diphosphonate is the best choice when labeling with Re-188. In this study, we labeled methylene diphosphonate (MDP), hydroxyethylidene diphosphonate (HEDP), and hydroxymethane diphosphonate (HDP) with Re-188. Each radiopharmaceutical was further evaluated in two conditions (with and without carrier). Twenty-four rabbits were used (four in each group) for the analysis of the biodistributions and bone uptakes of these radiopharmaceuticals to assess their potential for clinical applicability. Four hours after intravenous injection of approximately 37 MBq (1 mCi) Re-188-labeled diphosphonate preparations, whole body scans were performed using a large-field gamma camera equipped with a high resolution collimator. Bone-to-soft tissue ratios (B/S ratio) were calculated using a computer program. Our data showed that Re-188 HEDP with carrier (10(-4) M carrier) could accumulate in the skeletal system whereas very little absorption by bone was observed in the rabbits that were injected with carrier-free Re-188 HEDP. In addition, no significant bone uptake was demonstrated for Re-188 MDP or Re-188 HDP, with or without carrier. The B/S ratio was 25.06 in the Re-188 HEDP with carrier group but less than 3 in the other groups. In conclusion, HEDP is the best choice among these three bone-seeking drugs when labeled with Re-188. But, it is necessary to add carrier when preparing Re-188 HEDP for the treatment of bone metastases.
Nuclear Medicine and Biology, May 1, 1999
Rhenium-186 (Re-186) hydroxyethylidene diphosphonate (HEDP) has been shown to localize in metasta... more Rhenium-186 (Re-186) hydroxyethylidene diphosphonate (HEDP) has been shown to localize in metastatic foci within bone in a manner similar to Tc-99m bone-seeking agents. Usually, in the preparation of diagnostic Tc-99m radiopharmaceuticals, the concentration of Tc is at trace level (10(-8) M). However, large amounts of carrier are included in the preparation of Re-186 radiopharmaceuticals (10(-4) M), which may significantly affect the preparation of Re-HEDP. In this study, Re-188 was used as an Re tracer. The effects of pH and concentrations of Re carrier on the preparation of Re-HEDP were investigated. Re-188-Sn-HEDP was prepared by reconstitution of a kit of lyophilized HEDP mixture, and tin chloride with a radioactive solution of perrhenate in saline. The total concentration of Re present in this work ranged from 10(-8) to 10(-3) M. The results showed that high labeling efficiency was obtained for each preparation. Although the chemical behaviors of the Re-188 HEDP complexes, with and without carrier, were similar, the biodistribution patterns of carrier free Re-188 HEDP in rats were found to differ from the biodistribution patterns of carrier-added Re-188 HEDP.
PubMed, Mar 1, 2001
The aim of this study was to use brain SPECT to differentiate vascular parkinsonism (VP) from Par... more The aim of this study was to use brain SPECT to differentiate vascular parkinsonism (VP) from Parkinson's disease. Methods: Fourteen VP patients (age range, 59-87 y; mean age, 70 +/- 7.5 y), 30 Parkinson's disease patients (age range, 54-84 y; mean age, 65 +/- 8.8 y), and 26 healthy (control) individuals (age range, 50-85 y; mean age, 60 +/- 9 y) were examined. A 925-MBq (25 mCi) dose of (99m)Tc-TRODAT-1 was injected intravenously, and brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific striatal (99m)Tc-TRODAT-1 binding was measured and compared. Results: After a region-of-interest analysis of the images from VP patients, Parkinson's disease patients, and healthy volunteers was performed to obtain ratios of putamen to occipital and striatal to occipital binding as a measurement of specific binding to the dopamine transporters in these regions of the brain, where dopamine neurons are concentrated, the specific binding in the 14 VP patients was slightly lower than but not statistically different from that of the healthy individuals in both putamen and caudate areas. A significant decrease in uptake of (99m)Tc-TRODAT-1 in the striatum (P<0.01) was found in Parkinson's disease patients. Reduction of the uptake was more pronounced in the contralateral putamen of Parkinson's disease patients than that of VP patients (P<0.001). A significant bilateral striatal asymmetry was also observed in Parkinson's disease patients but not in VP patients (P< 0.01). Conclusion: Our findings clearly show that, for VP patients, (99m)Tc-TRODAT-1 SPECT is a reliable method to differentiate VP from Parkinson's disease. Further studies, including those to differentiate Parkinson's disease from arteriosclerotic parkinsonism and patients with both VP and Parkinson's disease, are needed to help rule out the possibility of Parkinson's disease as early as possible.
Applied Radiation and Isotopes, Dec 1, 1993
The separation of carrier-free 9oy from fission product WSr by solid supported solvent extraction... more The separation of carrier-free 9oy from fission product WSr by solid supported solvent extraction chromatography was investigated using Teflon grain as solid support and a di-(Zethylhexyl) phosphoric acid (D2EHPA) extraction agent as liquid phase. The optimum separation conditions are: (1) solid support using Dupont TFSOO Tetlon grains, (2) using 5% DZEHPA extraction agent as liquid phase, (3) setting the flow rate at 1 &/mm. and (4) using a column diameter of 0.5 cm which was packed with 1 g treated Teflon. After loading ?Sr/9oy equilibrium solution, the loaded column was washed with 0.3 N hydrochloric acid to remove ?Sr species; subsequently, 8 N hydrochloric acid was used as an eluent to obtain a 9oy solution. Chemical yield was about 90%; radionuclide impurity of ?Sr in the final product was < 10e6%. Consequently, the preparation of 1 mCi of 9oy was satisfactory for radiolabeling in medical applications. A radiotracer method using 05Sr and ssY was also developed to investigate separation efficiency.
Nuclear Medicine and Biology, Nov 1, 2004
Background: A novel radioiodine ligand [ 123 I] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5... more Background: A novel radioiodine ligand [ 123 I] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) has been suggested as a promising serotonin transporter (SERT) imaging agent for the central nervous system. In this study, the biodistribution of SERTs in the rabbit brain was investigated using [ 123 I] ADAM and mapping images of the same animal produced by both single-photon emission computed tomography (SPECT) and microautoradiography. A semiquantification method was adopted to deduce the optimum time for SPECT imaging, whereas the input for a simple fully quantitative tracer kinetic model was provided from arterial blood sampling data. Methods: SPECT imaging was performed on female rabbits postinjection of 185 MBq [ 123 I] ADAM. The time-activity curve obtained from the SPECT images was used to quantify the SERTs, for which the binding potential was calculated from the kinetic modeling of [ 123 I] ADAM. The kinetic data were analyzed by the nonlinear least squares method. The effects of the selective serotonin reuptake inhibitors fluoxetine and p-chloroamphetamine (PCA) on rabbits were also evaluated. After scanning, the same animal was sacrificed and the brain was removed for microautoradiography. Regions-of-interest were analyzed using both SPECT and microautoradiography images. The SPECT images were coregistered manually with the corresponding microautoradiography images for comparative study. Results: During the time interval 90-100 min postinjection, the peak specific binding levels in different brain regions were compared and the brain stem was shown to have the highest activity. The target-to-background ratio was 1.89F0.02. Similar studies with fluoxetine and PCA showed a background level for SERT occupation. Microautoradiography demonstrated a higher level of anatomical details of the [ 123 I] ADAM distribution than that obtained by SPECT imaging of the rabbit brain. Conclusion: SPECT imaging of the rabbit brain with [ 123 I] ADAM showed high affinity, high specificity, and favorable kinetics. The timeactivity curve showed that the accumulation of the [ 123 I] ADAM in the brain stem reached a maximum between 90 and 100 min postinjection. The microautoradiography provides high-resolution images of the rabbit brain. Our results for the [ 123 I] ADAM biodistribution in the rabbit brains demonstrate that this new radioligand is suitable as a selective SPECT imaging agent for SERTs.
Journal of Radioanalytical and Nuclear Chemistry, Sep 1, 1999
The evaluation of the pharmacokinetics of pure, beta radiopharmaceuticals is not possible with sc... more The evaluation of the pharmacokinetics of pure, beta radiopharmaceuticals is not possible with scintigraphy. Both whole-body autoradiography (WBAR) and Packard Instantimager, a device for rapid imaging, were used to study the whole body distribution of 7-and I~-emitting radionuclides (99mTc-MDP, 99mTc-sulftlr colloid, or ISSRe-HEDP), and results obtained from both methods were compared. The biodistribution of 99mTc-MDP and ISSRe-HEDP were seen mainly in bones including skull, spine, and vertebrae of spine and cardiac and skeletal muscles. The 99mTc-sulfur colloid localized in liver, bone marrow, and spleen. The resolution of WBAR is superior than that of Packard Instantimager. However, the advantage of Packard Instantimager is that rapid imaging within few minutes is possible with it, while WBAR imaging requires several hours to days.
Nuclear Medicine and Biology, Oct 1, 2001
In this study, the effectiveness of a 188 Re labeled sulfur colloid with two particle size ranges... more In this study, the effectiveness of a 188 Re labeled sulfur colloid with two particle size ranges was used to evalucate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. Methods: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10melanoma-bearing BDF 1 mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x10 5 B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (nϭ16ϳ18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes (Ͻ3m:80.4 Ϯ7.2%, colloid 1) and the other receiving larger particle sizes (Ͻ3m:12.3Ϯ1.0%, colloid 2). The animals were checked daily until death and their survival recorded. Results: Colloid 2 showed higher accumulation in almost all tissues, the highest accumulation organ was tumor (ϳ 40%), then spleen (ϳ20%), stomach (ϳ15%), diaphragm (ϳ3%), and liver (ϳ2%). There was a significant increase in survival time with increasing amount of the larger-particle-size colloid. Administered levels of 16-31 MBq/mouse were most efficacious and with higher amounts the survival times decreased significantly below that of the controls. There was a significant difference in the dose-response curves for the two preparations. Protection factors (1/Relative-risk) of nearly 5 were achieved using the larger colloid size, and nearly 30 using the smaller colloid size. An amount of 16-31 MBq of the colloid 2 was the optimal activity in these studies. On the one hand, the survival data agreed well with the biodistribution data, where higher accumulation was found in tumor with colloid 2. Conclusion: Rhenium-188 offers on-site availability, medium half-life, higher beta-particle energy of 2.12 MeV for therapy and emission of 155keV gamma photon suitable for imaging. The present study demonstrated that 188 Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals.
Applied Radiation and Isotopes, Mar 1, 1996
In this study we prepared and analyzed the biodistribution of 188Re-labelled Lipiodol ([188-Re]-L... more In this study we prepared and analyzed the biodistribution of 188Re-labelled Lipiodol ([188-Re]-Lipiodol) in rats after intrahepatic arterial injection. EDTB was synthesized by condensation of 1,2-benzenediamine and ethylenediaminetetraacetic acid (EDTA). The labelling efficiency of [188Re] Lipiodol was determined to be greater than 97% by ITLC developed with n-hexane. Following incubation of the [188Re] Lipiodol with an equal volume of serum
Nuclear Medicine and Biology, Nov 1, 1999
Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However... more Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However, its clinical value is reduced by a high restenosis rate. A new concept in preventing restenosis is the use of a liquid-filled balloon containing a beta-emitting radioisotope. In this study, we performed biodistribution studies of Re-188 perrhenate and Re-188 diethylenetriaminopentaacetate (DTPA) to assess the resulting organ dose values in the event of balloon rupture if these agents are used for the clinical inhibition of restenosis after percutaneous transluminal coronary angioplasty (PTCA). After injecting Re-188 preparations intravenously, rats were killed at 10 min, 30 min, 60 min, 2 h, and 6 h (n ؍ 5 per group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (%ID/g or %ID/mL). In addition, urine excretion and thyroid gland uptake were evaluated in rats (n ؍ 5 per group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed that both agents were excreted primarily via urine. However, the excretion of Re-188 DTPA was much faster than that of Re-188 perrhenate via the urinary system. The biodistribution data revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA group. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for both agents. The thyroid radiation value in the Re-188 perrhenate group was 0.163 mGy/MBq, which was much higher than that of the Re-188 DTPA group (0.0167 mGy/MBq). The stomach radiation value was as high as 0.127 mGy/MBq for Re-188 perrhenate, compared with 0.013 mGy/MBq for Re-188 DTPA. In conclusion, in the event of balloon rupture, the release of Re-188 DTPA results in lower radiation doses than Re-188 perrhenate, especially to the thyroid gland and the stomach. Our data suggest that Re-188 DTPA is a useful radiopharmaceutical for endovascular irradiation.
The Journal of Nuclear Medicine, May 1, 2011
International Journal of Molecular Sciences, Apr 8, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Radioanalytical and Nuclear Chemistry, Oct 1, 1998
ABSTRACT In recent years chances of using rhenium-186 and rhenium-188 as radioactive isotopes in ... more ABSTRACT In recent years chances of using rhenium-186 and rhenium-188 as radioactive isotopes in diagnostic and therapeutic applications are increased very much due to the characteristic radiochemical and chemical properties of these two radioisotopes. In particular, chemical similarities between99Tc and99mTc pair and186Re and188Re pair make it easier to correlate the two groups of compounds. Rhenium-188 is generated from the beta-decay of tungsten-188 which was produced by double neutron capture on enriched tungsten-186 oxide. It is of great interest to examine the impurities in the eluate by radiochemical neutron activation. For this purpose, the preconcentration of the impurities in samples were necessary, and it was achieved by adsorption on hydrated magnesium oxide.