177Lu-EDTMP for Treatment of Bone Pain in Patients with Disseminated Skeletal Metastases (original) (raw)
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Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
The purpose of the study was to assess the efficacy and safety profile of (177)Lu-EDTMP in patients with painful skeletal metastasis and make a comparative evaluation of the efficacy with that of (153)Sm-EDTMP. A total of 32 patients with painful skeletal metastases were prospectively evaluated (26 men and 6 women; mean age of 46.19 years; age range: 33-84 years). Patients were divided in two groups, Patients treated with (177)Lu-EDTMP (n = 16) and those treated with (153)Sm-EDTMP (n = 16). In both the groups, patients were treated with dose of 37MBq/kg body weight for both the radionuclide (dose range of (177)Lu-EDTMP varied from 1295 MBq to 2701 MBq depending on the weight of patient, whereas in (153)Sm-EDTMP the dose range varied from 1258 MBq to 2553 MBq). The following evaluation scores were adopted to examine the efficacy: [i] Analgesic score, [ii] pain scale (visual analogue scale or VAS), [iii] quality of life evaluation using 3 assessment scales (EORTC, Karnofsky and ECOG a...
Treatment efficacy of 153Sm-EDTMP for painful bone metastasis
http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. keyword: Radionuclide Therapy, Samarium, 153Sm-EDTMP, painful bone metastasis Introduction: Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. Methods: 28 patients (14 males and 14 females) aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. Results: 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks (mean±SD=15.22±7.8). 64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Over all response to therapy was 85.7%). The lowest amount of peripheral blood cells was detected in the fourth week for RBCs and in the 6th week for WBCs and PLTs. No one experienced hematological toxicity induced problems. Conclusion: Sm-153 lexidronam is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved. Ayati N et al. Asia Oceania J Nucl Med Biol. 2013;1(1) 153 Sm-EDTMP for metastatic bone pain Asia Oceania J Nucl Med Biol. 2013;1(1) 153 Sm-EDTMP for metastatic bone pain Research Institute (NSTRI). The other authors declare that they have no conflicts of interest.
153 Sm-EDTMP for bone pain palliation in skeletal metastases
European Journal of Nuclear Medicine and Molecular Imaging, 2004
153Sm-ethylene diamine tetramethylene phosphonate (EDTMP) is a widely available and extensively tested radiopharmaceutical for systemic radionuclide therapy in patients with symptomatic multiple skeletal metastases. Its use is approved for any secondary bone lesion which has been shown to accumulate 99mTc-methylene diphosphonate, including breast carcinoma. The molecule is stable in vitro and upon injection more than 50% of the dose is avidly fixed by lesional and non-lesional bone, with the rest being rapidly eliminated unchanged via the urine. The short half-life (46.3 h), the relatively low-energy beta emissions (E ave=233 keV) and the gamma emission (103 keV) make 153Sm a very attractive radionuclide, allowing therapeutic delivery of short-range electrons at relatively high dose rates with external imaging to corroborate biodistribution and possible dosimetric estimates. For a standard dose of 2,590 MBq/70 kg, the estimated radiation dose to metastases is 86.5 Gy. Critical organs are the bladder wall (2.5 Gy/2,590 MBq) and red marrow (4 Gy/2,590 MBq), with the latter being the critical factor in clinical practice as the dose-limiting factor is marrow radiotoxicity. The therapy has, however, proved safe provided that the platelet count exceeds 100×109/l and the white blood cell count exceeds 3.5×109/l. Clinical data obtained in fewer than 250 patients, within several studies, lead to the following conclusions: a dose of 37 MBq/kg has a better therapeutic ratio than a dose of 18.5 MBq/kg; the mean pain palliation rate after a single treatment in breast cancer is about 80%; toxicity is generally mild and transitory; and re-treatments are effective and safe provided that haematological values have fully recovered.
Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low β− energy, 177Lu [T1/2=6.73 days, Eβmax=497 keV, Eγ=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of 177Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: 177Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of 177Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: 177Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1–3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of 177Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing 177Lu does not alter its biological behaviour as a specific bone-seeking tracer. Species-specific pharmacokinetic behavior differences were observed. Toxicity studies in dogs did not show any biological adverse effects. The studies demonstrate that 177Lu-EDTMP is a promising radiopharmaceutical that can be further evaluated for establishing as a radiopharmaceutical for human use.
Pharmacokinetic, Dosimetry and Toxicity Study of 177Lu-EDTMP in Patients: Phase 0/I Study
177 Lu-EDTMP has been proposed as a potent bone pain palliation agent owing to theoretical advantage of reduced bone marrow suppression resulting from the low-energy and a suitably long half-life facilitating its wider distribution with less loss from radioactive decay. Herein, we report the pharmacokinetics, dosimetry and toxicity analysis of 177 Lu-EDTMP in patients (phase-0/I study). In a phase-0 study, the biokinetics of skeletal and non-skeletal uptake of 177 Lu-EDTMP was assessed in 6 patients with metastatic prostate cancer using tracer doses (172.7–206.9MBq). Data of whole skeletal uptake, blood and fractionated urine samples were obtained and dosimetric calculations were performed using the OLINDA/EXM 1.0 software. Prolonged bone retention was observed in all patients. Excretion was mainly via the renal route and blood clearance was rapid and biphasic. Mean estimated red marrow dose was 0.80±0.15mGy/MBq while mean total-body dose was 0.16±0.04mGy/MBq. A maximum tolerated dose (MTD) of 2000-3250MBqfor 177 Lu-EDTMP was calculated. For the phase-I study, 21 patients with metastatic prostate cancer were given a therapeutic dose of 177 Lu-EDTMP (692-5550MBq). Toxiciy (WHO), evaluated by assessment of hemoglobin levels, platelet and leukocyte counts over 12 weeks, was mainly limited to anemia or thrombocytopenia. Only transient toxicity was observed in 14/21 patients, of which 6 had baseline toxicity. Beyond the MTD, a significantly higher number of patients displayed grade 3-4 toxicity. Pain relief, assessed by VAS pain score, was observed in 86% patients with median relief duration of 7 weeks. The results demonstrate that 177 Lu-EDTMP has excellent pharmacokinetic and dosimetric properties, besides being safe and effective. Along with estimating radiation dose values to certain critical organs, we have also proposed an MTD for 177 Lu-EDTMP that correlated well with toxicity data. The encouraging dosimetry and toxicity data of 177 Lu-EDTMP reported provide the basis for subsequent phases of the studies to establish complete effectiveness and safety of 177 Lu-EDTMP as an attractive alternative to other radioactive bone pain palliation agents.
Asia Oceania journal of nuclear medicine & biology, 2015
Objective(s): Recently, bone-avid radiopharmaceuticals have been shown to have potential benefits for the treatment of widespread bone metastases. Although 177Lutriethylene tetramine hexa methylene phosphonic acid (abbreviated as 177Lu- TTHMP), as an agent for bone pain palliation, has been evaluated in previous studies, there are large discrepancies between the obtained results. In this study, production, quality control, biodistribution, and dose evaluation of 177Lu-TTHMP have been investigated and compared with the previously reported data. Methods: TTHMP was synthesized and characterized, using spectroscopic methods. Radiochemical purity of the 177Lu-TTHMP complex was determined using instant thin-layer chromatography (ITLC) and high performance liquid chromatography (HPLC) methods. The complex was injected to wild-type rats and biodistribution was studied for 7 days. Preliminary dose evaluation was investigated based on biodistribution data in rats. Results: 177Lu was prepared ...
Journal of Radioanalytical and Nuclear Chemistry, 2014
In this work, the cocktail complex 153 Sm/ 177 Lu-EDTMP was prepared in high radiochemical purity (more than 99 %) using in house synthesized EDTMP ligand for obtaining a possible synergistic wide range palliative agent. The mixture was administered to wild-type rats and biodistribution data collected after 2 h to 7 days showed at least 70 % accumulation of the radioactivity in the bone tissues. Scintigraphic images were taken from wild-type rats injected with 153 Sm/ 177 Lu-EDTMP after 24 h and the biodistribution was shown to be consistent with post-mortem data. A comparative accumulation study was performed for vital organs up to 7 days. 153 Sm/ 177 Lu-EDTMP seemed a promising agent for bone pain palliation therapy in skeletal metastases in humans as a novel combined radiopharmaceutical.