Examining Absorbed Doses of Indigenously Developed <sup>177</sup>Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer Patients at Baseline and During Course of Peptide Receptor Radioligand Therapy

Kamaldeep,; Wanage, Gaurav; Sahu, Sudeep; Maletha, Pravind; Adnan, Aadil; Suman, Sonam; Basu, Sandip; Das, Tapas; Banerjee, Sharmila

doi:10.1089/cbr.2020.3640

Cited by 17 publications

(10 citation statements)

References 25 publications

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“…Recent work has shown high tumor doses for skeletal, lymph node, and liver metastases [74], and in some (prospective) studies for lung metastases as well [75] in patients administered with [ 177 Lu]Lu-PSMA-617. Radiation dosimetry demonstrated high tumor absorbed doses, as shown in Table 2, and low exposure to OAR.…”

Section: Tumor Lesion Dosimetrymentioning

confidence: 99%

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Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

et al. 2022

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In light of widely expanding personalized medicine applications and their impact on clinical outcomes, it is naturally befitting to explore all the dimensional aspects of personalized radionuclide therapy (RNT). Adoption of absorbed radiation dose into clinical practice in the field of RNT has been hampered by difficulties such as evidence of dose-effect correlation, technical requirements in quantitative imaging of the radiopharmaceutical, heterogeneity of methods between not only centers, but also across software, hardware and radionuclides used. Additionally, standardized agreed upon definition of outcome measures is being debated whether it be solely related to toxicity, quality of life, survival or other measures. Many clinical RNT activity administrations are still based on empirical/fixed activities, or scaled based on parameters such as body surface area. Although still challenging, a tremendous amount of progress has been made to facilitate routine clinical dosimetry with discussions regarding standardization, harmonization and automated processing techniques. This has also been aided by the development and FDA approval of several companion diagnostics allowing within the theranostic paradigm not only a crude qualitative predictive biomarker but also an objective dosimetry based predictive therapeutic biomarker. This work aims to review the literature of [177Lu]Lu-PSMA RNT, focusing on clinical trials and studies, with the goal to summarize the range of dosimetry techniques and the range of doses calculated to organs and tissues of interest from these techniques. A dosimetry method for [177Lu]Lu-PSMA RNT should be reliable, reproducible and encompassing the knowledge gained from all clinical trials evaluating it. Its translation into clinical routine practice can be achieved with the confirmation that dose calculation represents good clinical efficacy and low treatment-related toxicity. Finally, some future perspectives on the future of [177Lu]Lu-PSMA RNT are made, especially in the rapidly emerging field of artificial intelligence (AI), where deep learning may be able to play a large role in the simplification of dosimetry calculations to aid in their clinical adoption.

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Section: Tumor Lesion Dosimetrymentioning

confidence: 99%

“…Various studies have reported on absorbed doses to normal organs and tissues [74,75,76,77,89,92], as is shown in Table 3.…”

Section: Normal Organ and Tissue Dosimetrymentioning

confidence: 99%

Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

et al. 2022

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“…Unlike anti-CD20 antibody for non-Hodgkins’ lymphoma, it is unclear whether unconjugated anti-PSMA antibody and small molecular inhibitors themselves have any clinically significant anti-tumor effects which could complicate dose response evaluation for radiolabeled agents [ 68 ]. So far, several post-therapy dosimetry studies have shown a trend of dose response to 177 Lu-PSMA-617 treatment in mCRPC patients [ [69] , [70] , [71] , [72] ]. Violet et al .…”

Section: Psma Targeted Radiopharmaceutical Therapy (Rpt)mentioning

confidence: 99%

PSMA theragnostics for metastatic castration resistant prostate cancer

Song

Guja

Iagaru

2022

Translational Oncology

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“…Literature data for kidney dosimetry can be summarized as for beta emitters 177 Lu-PSMA-617 0.01–0.11 mGy/MBq [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ], 177 Lu-PSMA-I&T 0.72 mGy/MBq [ 53 ], and 177 Lu-DOAT ZOL 0.49 mGy/MBq [ 54 ] and for alpha emitters 225 Ac-PSMA-617 0.7 mSv/MBq [ 39 ] and 213 Bi-PSMA-617 8.1 mSv/MBq [ 55 ].…”

Section: Peptide Receptor Radionuclide and Radioligand Therapymentioning

confidence: 99%

Kidney Protection with the Radical Scavenger α1-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy

et al. 2021

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α1-microglobulin (A1M) is an antioxidant found in all vertebrates, including humans. It has enzymatic reductase activity and can scavenge radicals and bind free heme groups. Infused recombinant A1M accumulates in the kidneys and has therefore been successful in protecting kidney injuries in different animal models. In this review, we focus on A1M as a radioprotector of the kidneys during peptide receptor radionuclide/radioligand therapy (PRRT/RLT). Patients with, e.g., neuroendocrine tumors or castration resistant prostate cancer can be treated by administration of radiolabeled small molecules which target and therefore enable the irradiation and killing of cancer cells through specific receptor interaction. The treatment is not curative, and kidney toxicity has been reported as a side effect since the small, radiolabeled substances are retained and excreted through the kidneys. In recent studies, A1M was shown to have radioprotective effects on cell cultures as well as having a similar biodistribution as the somatostatin analogue peptide 177Lu-DOTATATE after intravenous infusion in mice. Therefore, several animal studies were conducted to investigate the in vivo radioprotective potential of A1M towards kidneys. The results of these studies demonstrated that A1M co-infusion yielded protection against kidney toxicity and improved overall survival in mouse models. Moreover, two different mouse studies reported that A1M did not interfere with tumor treatment itself. Here, we give an overview of radionuclide therapy, the A1M physiology and the results from the radioprotector studies of the protein.

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Examining Absorbed Doses of Indigenously Developed ¹⁷⁷Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer Patients at Baseline and During Course of Peptide Receptor Radioligand Therapy

Cited by 17 publications

References 25 publications

Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

PSMA theragnostics for metastatic castration resistant prostate cancer

Kidney Protection with the Radical Scavenger α1-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy

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Examining Absorbed Doses of Indigenously Developed 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer Patients at Baseline and During Course of Peptide Receptor Radioligand Therapy

Cited by 17 publications

References 25 publications

Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

PSMA theragnostics for metastatic castration resistant prostate cancer

Kidney Protection with the Radical Scavenger α1-Microglobulin (A1M) during Peptide Receptor Radionuclide and Radioligand Therapy

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Product

Resources

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Examining Absorbed Doses of Indigenously Developed ¹⁷⁷Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer Patients at Baseline and During Course of Peptide Receptor Radioligand Therapy