Practical dosimetry of peptide receptor radionuclide therapy with (90)Y-labeled somatostatin analogs (original) (raw)
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Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy
Annals of Oncology, 1999
Background: Peptide receptor scintigraphy with the radioactive somatostatin analogue, [ m In-DTPA 0 ]octreotide, is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumours. Aim: With this technique primary tumours and metastases of neuroendocrine cancers as well as of many other cancer-types can be localised. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy (PRRT) with repeated administrations of high doses of [ lu In-DTPA°]octreotide. '"in emits Auger and conversion electrons having a tissue penetration of 0.02-10 urn and 200 to 500 urn, respectively. Patients and methods: Thirty end-stage patients with mostly neuroendocrine progressing tumours were treated with [ ul In-DTPA°]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. Results: There were no major clinical side effects after up to two years treatment, except that in a few patients a transient decline in platelets counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight patients showed stabilisation of disease and six other patients a reduction in size of tumours. There is a tendency towards better results in patients whose tumours have a higher accumulation of the radioligand. Conclusions: PRRT is feasible, also with m I n as radionuclide. Depending on the homogeneity of distribution of tumour cells expressing peptide receptors and the size of the tumour, P-emitting radionuclides, e.g., 90 Y, labelled to DOTAchelated peptides, are also attractive candidates for PRRT. The first PRRT trials with [ 90 Y-DOTA°,Tyr 3 ]octreotide started recently.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2018
Pre-therapy PET imaging with Y-DOTATOC PET is considered the ideal dosimetry protocol for Y-DOTATOC therapy; however, its cost, low availability and the need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. To develop a dosimetric method for Y-DOTATOC therapy using Y-DOTATOC PET/CT and Bremsstrahlung SPECT/CT imaging and to determine if dosimetry-based administered activities differed significantly from standard administered dosages. This is a prospective Phase 2 trial of Y-DOTATOC therapy in patients with somatostatin receptor positive tumors. Y-DOTATOC is given in 3 cycles 6-8 weeks apart. All adult subjects receive 4.4 GBq and pediatric patients receive 1.85 GBq/m2 in the first cycle of therapy; the subsequent dosages of Y-DOTATOC are adjusted based on the dosimetry of the preceding cycle not to exceed a total kidney dose of 23 Gy and bone marrow dose of 2 Gy. The radiation dose to the kidneys was determined from serial imagin...
Journal of Nuclear Medicine Official Publication Society of Nuclear Medicine, 2005
A new treatment modality for inoperable or metastasized gastroenteropancreatic tumors is the use of radiolabeled somatostatin analogs. Initial studies with high doses of [ 111 In-diethylenetriaminepentaacetic acid (DTPA) 0 ]octreotide in patients with metastasized neuroendocrine tumors were encouraging, although partial remissions were uncommon. Another radiolabeled somatostatin analog that is used for peptide receptor radionuclide therapy (PRRT) is [ 90 Y-1,4,7,10-tetraazacyclododecane-N,NЈ,NЉ,Nٞ-tetraacetic acid (DOTA) 0 ,Tyr 3 ]octreotide. Various phase 1 and phase 2 PRRT trials have been performed with this compound. Despite differences in the protocols used, complete and partial remissions in most of the studies with [ 90 Y-DOTA 0 ,Tyr 3 ]octreotide were in the same ranges, 10%-30%; these ranges were higher than those obtained with [ 111 In-DTPA 0 ]octreotide. Treatment with the newest radiolabeled somatostatin analog, [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate, which has a higher affinity for the subtype 2 somatostatin receptor, resulted in complete or partial remissions in 30% of 76 patients. Tumor regression was positively correlated with a high level of uptake on OctreoScan imaging, a limited hepatic tumor mass, and a high Karnofsky performance score. Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumors. Symptomatic improvement may occur with all 111 In-, 90 Y-, or 177 Lu-labeled somatostatin analogs that have been used for PRRT. The results obtained with [ 90 Y-DOTA 0 ,Tyr 3 ]octreotide and [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the duration of the therapy response for both radiopharmaceuticals is more than 2 y. These data compare favorably with those for the limited number of alternative treatment approaches.
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.
European Journal of Nuclear Medicine and Molecular Imaging, 1999
dent differences in uptake of radiolabelled [DOTA 0 , Tyr 3 ]octreotide, being the resultant of a positive effect of increasing amounts of peptide on, for example, receptor clustering and a negative effect of receptor saturation, are of consequence for rat radionuclide therapy studies with radiolabelled peptides and may also be of consequence for human radionuclide therapy studies with this compound. & k w d : Key words: [DOTA 0 ,Tyr 3 ]octreotide -Somatostatin receptors -Tumour uptake -Peptide mass Eur J Nucl Med (1999) 26:693-698 Recently [Tyr 3 ]octreotide, which has a higher binding affinity for the sst 2 than octreotide, was derivatized with the chelator DOTA, enabling stable radiolabelling with
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
Preclinical and clinical studies have indicated that somatostatin receptor (sst)-expressing tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst agonists. In 4 consecutive patients with advanced neuroendocrine tumors, we evaluated whether treatment with (177)Lu-labeled sst antagonists is feasible. After injection of approximately 1 GBq of (177)Lu-DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2] ((177)Lu-DOTA-JR11) and (177)Lu-DOTATATE, 3-dimensional voxel dosimetry analysis based on SPECT/CT was performed. A higher tumor-to-organ dose ratio for (177)Lu-DOTA-JR11 than for (177)Lu-DOTATATE was the prerequisite for treatment with (177)Lu-DOTA-JR11. Reversible minor adverse effects of (177)Lu-DOTA-JR11 were observed. (177)Lu-DOTA-JR11 showed a 1.7-10.6 times higher tumor dose than (177)Lu-DOTATATE. At the same time, the tumor-to-kidney and tumor-to-bone marrow dose ratio was 1.1-7.2 times higher. All 4 patients were treated with (177)Lu-DOTA-JR11, resul...
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.
Clinical and translational imaging, 2014
Peptide receptor radionuclide therapy (PRRT) has been shown to be an effective treatment for neuroendocrine tumors (NETs) if curative surgery is not an option. A majority of NETs abundantly express somatostatin receptors. Consequently, following administration of somatostatin (SST) analogs labeled with γ-emitting radionuclides, these tumors can be imaged for diagnosis, staging or follow-up purposes. Furthermore, when β-emitting radionuclides are used, radiolabeled peptides (radiopeptides) can also be used for the treatment for NET patients. Even though excellent results have been achieved with PRRT, complete responses are still rare, which means that there is room for improvement. In this review, we highlight some of the directions currently under investigation in pilot clinical studies or in preclinical development to achieve this goal. Although randomized clinical trials are still lacking, early studies have shown that tumor response might be improved by application of other radio...
Seminars in nuclear medicine, 2002
Fifty patients with somatostatin receptor-positive tumors were treated with multiple doses of [(111)In-diethylenetriamine pentaacetic acid(0)]octreotide. Forty patients were evaluable after cumulative doses of at least 20 GBq up to 160 GBq. Therapeutic effects were seen in 21 patients: partial remission in 1 patient, minor remissions in 6 patients, and stabilization of previously progressive tumors in 14 patients. Our results thus underscore the therapeutic potential of Auger-emitting radiolabelled peptides. The toxicity was generally mild bone marrow toxicity, but 3 of the 6 patients who received more than 100 GBq developed a myelodysplastic syndrome or leukemia. Therefore, we consider 100 GBq as the maximal tolerable dose. With a renal radiation dose of 0.45 mGy/MBq (based on previous studies) a cumulative dose of 100 GBq [(111)In-DTPA(0)]octreotide will lead to 45Gy on the kidneys, twice the accepted limit for external beam radiation. However, no development of hypertension, prot...