Calculation of absorbed dose due to the 90Y-DOTATOC peptide receptor radionuclide therapy by MCNP5/X (original) (raw)
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Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients that are expected to benefit from PRRT and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors (PNETs) treated with PRRT using 177 Lu-DOTATATE. Methods Tumor absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized PNETs treated with repeated cycles of 177 Lu-DOTATATE at 8 weeks intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96 and 168 h after infusion of 177 Lu-DOTATATE. The unit density sphere model from Organ Level Internal Dose Assessment (OLINDA) was used for absorbed dose calculations. The absorbed doses were corrected for partial volume effect (PVE) based on phantom measurements. Based on these results, only tumors larger than 2.2 cm diameter at any time during the treatment were included for analysis. To further decrease the effect of PVE, a subgroup of tumors (larger than 4 cm) were analysed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors (RECIST). Results Tumor absorbed doses until best response ranged approximately from 10 to 340 Gy. A two parameter sigmoid fit was fitted to the data and a significant correlation between the absorbed dose and tumor reduction was found, with Pearson correlation coefficient (R 2) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4 cm. The largest tumor reduction was 57% after a total absorbed dose of 170 Gy. Conclusion The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses.
In Vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy
PloS one, 2017
Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET) nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-LET type of exposure. Affinities of DOTA-DPhe1-Tyr3-octreotate (DOTATATE), 115In-DOTATATE, 175Lu-DOTATATE and 209Bi-DOTATATE were determined in the K562-SST2 cell line. Two other cell lines were used for radiation response assessment; BON and CA20948, with a low and high expression of somatostatin receptors, respectively. Cellular uptake kinetics of 111In-DOTATATE were determined in CA20948 cells. CA20948 and BON were irradiated with 137Cs, 177Lu-DTPA, 177Lu-DOTATATE, 213Bi-DTPA and 213Bi-DOTATATE. Absorbed doses were calculated using the MIRDcell dosimetry method for the specific binding and a Monte Car...
Differences in predicted and actually absorbed doses in peptide receptor radionuclide therapy
Medical Physics, 2012
Purpose: An important assumption in dosimetry prior to radionuclide therapy is the equivalence of pretherapeutic and therapeutic biodistribution. In this study the authors investigate if this assumption is justified in sst2-receptor targeting peptide therapy, as unequal amounts of peptide and different peptides for pretherapeutic measurements and therapy are commonly used. Methods: Physiologically based pharmacokinetic models were developed. Gamma camera and serum measurements of ten patients with metastasizing neuroendocrine tumors were conducted using 111 In-DTPAOC. The most suitable model was selected using the corrected Akaike information criterion. Based on that model and the estimated individual parameters, predicted and measured 90 Y-DOTATATE excretions during therapy were compared. The residence times for the pretherapeutic (measured) and therapeutic scenarios (simulated) were calculated. Results: Predicted and measured therapeutic excretion differed in three patients by 10%, 31%, and 7%. The measured pretherapeutic and therapeutic excretion differed by 53%, 56%, and 52%. The simulated therapeutic residence times of kidney and tumor were 3.1 ± 0.6 and 2.5 ± 1.2 fold higher than the measured pretherapeutic ones. Conclusions: To avoid the introduction of unnecessary inaccuracy in dosimetry, using the same substance along with the same amount for pretherapeutic measurements and therapy is recommended.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients who are expected to benefit from PRRT, and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors treated with PRRT using (177)Lu-DOTATATE. Tumor-absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE at 8-wk intervals. The absorbed dose calculations relied on sequential SP...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
A novel radio guided surgery (RGS) technique exploiting β- radiation has been proposed. To develop such technique, a suitable radio-tracer able to deliver a β- emitter to the tumor has to be identified. A first candidate is represented by (90)Y-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid0-D-Phe1,Tyr3]octreotide (DOTATOC), a compound commonly used today for peptide radio-receptor therapy. The application of this β- -RGS to neuroendocrine tumors (NET) requires to study the uptake of DOTATOC and its time evolution both in tumors and healthy organs, and to evaluate the corresponding performances of the technique. the uptake of lesions and healthy organs (kidneys, spleen, liver and healthy muscle) was estimated on (177)Lu-DOTATOC SPECT/CT scans of 15 patients affected by NET with different localizations, treated at IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. For each patient SPECT/CT images, acquired at 0.5, 4, 20, 40 and ...
Journal of Nuclear Medicine, 2013
(68)Ga-DOTATOC and (68)Ga-DOTATATE are 2 radiolabeled somatostatin analogs for in vivo diagnosis of neuroendocrine tumors with PET. The aim of the present work was to measure their comparative biodistribution and radiation dosimetry. Ten patients diagnosed with neuroendocrine tumors were included. Each patient underwent a 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 3 h after injection of each tracer on consecutive days. Absorbed doses were calculated using OLINDA/EXM 1.1. Data from 9 patients could be included in the analysis. Of the major organs, the highest uptake at 1, 2, and 3 h after injection was observed in the spleen, followed by kidneys and liver. For both tracers, the highest absorbed organ doses were seen in the spleen and urinary bladder wall, followed by kidney, adrenals, and liver. The absorbed doses to the liver and gallbladder wall were slightly but significantly higher for (68)Ga-DOTATATE. The total effective dose was 0.021 ± 0.003 mSv/MBq for both tracers. The effective dose for a typical 100-MBq administration of (68)Ga-DOTATATE and (68)Ga-DOTATOC is 2.1 mSv for both tracers. Therefore, from a radiation dosimetry point of view, there is no preference for either tracer for PET/CT evaluation of somatostatin receptor-expressing tumors.
Practical dosimetry of peptide receptor radionuclide therapy with (90)Y-labeled somatostatin analogs
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2005
The challenge for internal therapy is to deliver the highest possible dose to the tumor while sparing normal organs from damage. Currently, the potential risk of kidney and red marrow toxicity limits the amount of radioactivity that may be administered. An accurate dosimetry method that would provide reliable dose estimates to these critical organs and to tumors before therapy would allow the clinician to plan a specific therapeutic regimen and also select those patients who would benefit the most from treatment. The dosimetry for (90)Y-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide is usually based on quantitative imaging at different time points that provides information on activity retention in organs over time and on stylized models representing average individuals. Because the therapeutic agent labeled with (90)Y is not suitable for quantitative imaging, the peptide surrogate labeled with the positron emitter (86...
Clinical Cancer Research, 2008
Peptide receptor radionuclide therapy (PRRT) using somatostatin analogues labeled with h-particle^emitting isotopes such as 90 Yor 177 Lu has been a promising treatment strategy for metastasized neuroendocrine tumors. Although remission can be accomplished in a high percentage of neuroendocrine tumors, some tumors do not respond to this treatment. a-Emitting isotopesösuch as the 10-day half-life a-emitting generator nuclide Actinum-225 (225 Ac)öare characterized by extremely high cytotoxic activity on the cellular level, and may be superior in the treatment of neuroendocrine tumors not responding to PRRTusing h-emitting isotopes. Experimental Design: Radiolabeling of 225 Ac 1,4,7,10-tetra-azacylododecane N,N ¶,N ¶ ¶,N ¶ ¶ ¶-Jtetraacetic acid-Tyr 3-octreotide (DOTATOC) was done at pH 5 (60 minutes at 70jC) without further purification. Biodistribution in nude mice bearing AR42J rat pancreas neuroendocrine tumor xenografts were measured for up to 24 hours. Toxicity was tested by weight changes, retention variables (blood urea nitrogen and creatine), and histopathology in mice 7 months after treatment with 10 to 130 kBq (n = 4-5). Therapeutic efficacy was assessed by tumor weighing in animals treated 4 days after xenotransplantation and compared with 177 Lu-DOTATOC as a reference. Results: Activities up to 20 kBq had no significant toxic effects in mice. In contrast, activities higher than 30 kBq induced tubular necrosis. Biodistribution studies revealed that 225 Ac-DOTA-TOC effectively accumulated in neuroendocrine xenograft tumors. 225 Ac-DOTATOC activities were shown to be nontoxic (12-20 kBq), reduced the growth of neuroendocrine tumors, and showed improved efficacy compared with 177 Lu-DOTATOC. Conclusions: 225 Ac might be suitable to improve PRRT in neuroendocrine tumors.
Dosimetric comparison of radionuclides for therapy of somatostatin receptor-expressing tumors
International Journal of Radiation Oncology*Biology*Physics, 2001
Purpose: Therapy of tumors expressing somatostatin receptors, sstr, has recently been clinically tested using somatostatin analogues labeled with 111 In and 90 Y. Several other radionuclides, i.e., 131 I, 161 Tb, 64 Cu, 188 Re, 177 Lu, and 67 Ga, have also been proposed for this type of therapy. The aim of this work was to investigate the usefulness of the above-mentioned radionuclides bound to somatostatin analogues for tumor therapy. Methods: Biokinetic data of 111 In-labeled octreotide in mice and man were used, primarily from our studies but sometimes from the literature. Dosimetric calculations were performed with the assumption that biokinetics were similar for all radionuclides bound to somatostatin analogues. The cumulated tumor:normal-tissue activity concentration, TNC , was calculated for the various physical half-lives of the radionuclides. Using mathematical models, the tumor:normal-tissue mean absorbed dose rate ratio, TN Ḋ , and tumor:normal-tissue mean absorbed dose ratio, TND, were calculated for various tumor sizes in mice and humans. Results: TNC of radionuclide-labeled octreotide increased with physical half-life for most organs, both in mice and in humans. TN Ḋ showed that radionuclides emitting electrons with too high energy are not suitable for therapy of small tumors. Furthermore, radionuclides with a higher frequency of photon emissions relative to electron emissions will yield lower TN Ḋ and are thus less suitable for therapy than radionuclides with a lower frequency of photon emissions. The TND was highest for 161 Tb in both mice and humans. Conclusions: The results demonstrate that long-lived radionuclides, which emit electrons with rather low energy and which have low frequency of photon emissions, should be the preferred therapy for disseminated small sstr-expressing tumors.
Dosimetry in Peptide radionuclide receptor therapy: a review
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2006
The potential of targeted therapy with radiolabeled peptides has been reported in several clinical trials. Although there have been many improvements in dose estimation, a general and reliable dosimetric approach in peptide receptor radionuclide therapy (PRRT) is still a matter of debate. This article reviews the methods for PRRT dosimetry and the results presented in the literature. Radiopharmaceutical characteristics, data processing, dosimetric outcomes, and methods to protect critical organs are reported. The biological effective dose, based on the linear quadratic model, is also described.