Dosimetry for 177Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer

Delker, Andreas; Fendler, Wolfgang P.; Kratochwil, Clemens; Brunegraf, Anika; Gosewisch, Astrid; Gildehaus, Franz Josef; Tritschler, Stefan; Stief, Christian G.; Kopka, Klaus; Haberkorn, Uwe; Bartenstein, Peter; Böning, Guido

doi:10.1007/s00259-015-3174-7

Cited by 267 publications

(426 citation statements)

References 37 publications

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“…Those men with progressive disease who do not respond to 177 Lu PSMA therapy range from 10% to 32%. One of the larger studies, with 56 men enrolled, had 80% of all men enrolled had a PSA response to therapy3 All currently published studies with 177 Lu PSMA therapy in prostate cancer are retrospective, mostly single arm, and involve a variety of treatment regimens, both in terms of dose given (ranging from 3.5 to 8.0 Gbq/injection of Lu PSMA) and the number of doses administered (ranges from a single injection up to 4–6 injections 6 weeks apart) 2, 3, 4, 5, 6, 8, 9, 27, 39. This makes interpretation of the efficacy of the treatment difficult at this stage.…”

Section: Treatment Efficacymentioning

confidence: 99%

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Emmett

Willowson

Violet

et al. 2017

J of Medical Radiation Sci

255

233

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Prostate‐specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high‐binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides. Early clinical studies evaluating the safety and efficacy of Lu PSMA therapy have demonstrated promising results with a significant proportion of men with metastatic prostate cancer, who have already failed other therapies, responding clinically to Lu PSMA. This review discusses the practical issues of administering Lu PSMA, and gives an overview of the findings from currently published trials in regards to treatment response rates, expected toxicities and safety.

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Section: Treatment Efficacymentioning

confidence: 99%

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Emmett

Willowson

Violet

et al. 2017

J of Medical Radiation Sci

255

233

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show abstract

“…0.03 Gy/GBq) and kidneys (approx. 0.6 Gy/GBq) should be considered as dose limiting organs (6)(7)(8)18,19). (14) and despite moderate xerostomia there is no evidence of relevant treatment-related toxicity.…”

Section: Responsementioning

confidence: 99%

“…Coupling with DOTA enables labeling with several diagnostic and therapeutic radionuclides (5). Different centers (6)(7)(8) reported favorable dosimetry for 177 Lu-PSMA-617, which in regard to kidney (approx. 0.6 Gy/GBq) and red marrow dose (approx.…”

Section: Introductionmentioning

confidence: 99%

Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

et al. 2017

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Current treatment protocols for 177Lu-PSMA-617 therapies were cautiously derived from dosimetry data, but their practical appropriateness have not yet been proven clinically.We retrospectively report our clinical observations using four different treatment activities. Methods: Forty patients with advanced prostate cancer and positive uptake in PSMA-imaging were treated in fractions of 4 GBq / 80 nmol, 6 GBq / 120 nmol, 7.4 GBq / 150 nmol or 9.3 GBq / 150 nmol 177 Lu-activity / precursor-amount (n=10, respectively) every 2 months. Safety lab was checked every 2 weeks, PSA-response every 4 weeks; other effects were assessed per anamnesis. Results: Initial PSA response presented no correlation to treatment activity. However, 2/10, 4/10, 4/10 and 7/10 patients with doses of 4, 6, 7.4 and 9.3 GBq were in partial remission 8 weeks after completing all 3 cycles;This would be in line with, but due to low patient numbers not proving, a positive doseresponse-relationship. Acute hematological toxicity was also irrespective of treatment activity and no more than one grade-3/4 toxicity was observed in each group.Nevertheless, in contrast to the other groups the mean platelet count in the 9. (8,12). Nevertheless, tolerance limits for normal organs reported in the literature are based on external beam radiotherapy and have only been extrapolated to RLT using radiobiological models, which themselves have manifold limitations as reviewed recently (13). Thus, dosimetry in nuclear medicine can only approximate a guidance level for dosing RLT but the optimal treatment regime has still to be refined clinically.In this retrospective analysis we report our clinical experience with fractions of 4 GBq, 6GBq, 7.4 GBq or 9.3 GBq 177 Lu-PSMA-617 repeated every 2 months.by on May 10, 2018. For personal use only. jnm.snmjournals.org Downloaded from MATERIALS AND METHODS Patients 177Lu-PSMA-RLT was performed under the conditions of the updated declaration of Helsinki, § 37 (Unproven interventions in clinical practice) and in accordance to the German Pharmaceuticals Law §13(2b) as a salvage therapy for patients with mCRPC, which had to be resistant against or ineligible for approved options and presented with progressive disease. Patient selection is outlined in Fig. 1. For patients stratified to 177 Lu-PSMA-617, each dose level was administered to 10 consecutive patients. If toxicities were comparable to the placebo group of the ALSYMPCA-trial (14), individual dose escalations for non-responders were considered ethically justified, resulting in a short learning-phase using heterogeneous dosing regimens between respective dose escalation groups. Data of these heterogeneous interim patients were not suitable for this kind of systematical evaluation, nevertheless some have been made public available within other publications (8,15). The chronology how this dose escalation was embedded into clinical practice is summarized in Fig. 2. Patient characteristics were summarized in (Table 1). All patients were informed about the experime...

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“…From a dosimetry standpoint, there is a wide inter-patient variability both in tumor and healthy tissues, including the salivary glands. The range of absorbed dose delivered to the salivary glands per administered activity 177 Lu-DKFZ-PSMA-617 varied from 0.8 to 2.5 Gy/GBq (4,7,8). Preventive strategies have not been successful in mitigating these side-effects of salivary gland function (local cooling, lemon juice and vitamin C, displacement strategy using PMPA) (9, 10).…”

mentioning

confidence: 99%

PSMA-Targeted Radionuclide Therapy and Salivary Gland Toxicity: Why Does It Matter?

Taïeb¹,

Foletti²,

Bardiès³

et al. 2018

J Nucl Med

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Dosimetry for 177Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer

Cited by 267 publications

References 37 publications

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

PSMA-Targeted Radionuclide Therapy and Salivary Gland Toxicity: Why Does It Matter?

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Dosimetry for 177Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer

Cited by 267 publications

References 37 publications

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Repeated 177Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

PSMA-Targeted Radionuclide Therapy and Salivary Gland Toxicity: Why Does It Matter?

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Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Lutetium ¹⁷⁷ PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq