Dosimetry in Lu-177-PSMA-617 prostate-specific membrane antigen targeted radioligand therapy: a systematic review

Abstract

Background 177Lu-prostate-specific membrane antigen (PSMA) gained popularity as a choice of agent in the treatment of patients with advanced prostate cancer or metastatic castration-resistant stage of prostate carcinoma (mCRPC) diseases. However, this treatment may cause fatal effects, probably due to unintended irradiation of normal organs. We performed an extensive systematic review to assess the organs at risk and the absorbed dose received by tumor lesions in 177Lu-PSMA therapy. Design In this review, published peer-reviewed articles that cover clinical dosimetry in patients following peptide radionuclide ligand therapy using 177Lu-PSMA have been included. Two senior researchers independently checked the articles for inclusion. A systematic search in the database was made using PubMed, Publons and DOAJ. All selected articles were categorized into three groups: (1) clinical studies with the technical description of dosimetry in 177Lu-PSMA therapy (2) organ dosimetry in 177Lu-PSMA therapy or (3) tumor dosimetry in 177Lu-PSMA therapy. Result In total, 182 citations were identified on PSMA therapy and 17 original articles on 177Lu-PSMA dosimetry were recognized as eligible for review. The median absorbed dose per unit of administered activity for kidneys, salivary, liver, spleen, lacrimal and bone marrow was 0.55, 0.81, 0.1, 0.1, 2.26 and 0.03 Gy/GBq, respectively. The median absorbed dose per unit of activity for tumor lesions was found in a range of 2.71–10.94 Gy/GBq. Conclusion 177Lu-PSMA systemic radiation therapy (SRT) is a well-tolerated and reliable treatment option against the management of the mCRPC stage of prostate carcinoma. Lacrimal glands and salivary glands are the major critical organs in 177Lu-PSMA SRT. Besides, tumors receive 3–6 times higher absorbed doses compared to organs at risk.

Dual-Time-Point Posttherapy177Lu-PSMA-617 SPECT/CT Describes the Uptake Kinetics of mCRPC Lesions and Prognosticates Patients’ Outcome

“…Existing data on 177 Lu-PSMA-617 RLT dosimetry indicate that the radiation dose delivered to the target is key in ensuring response (21,22). However, in a recent systematic review, a relevant variability in tumor dose (range, 7.5-77.6 Gy) was highlighted across and within populations (23). Technical issues and differences in tracer uptake intensity could partly account for this variability.…”

Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT)

“…Similar absorbed doses to organs-at-risk have also been approximated when using [ 177 Lu]Lu-PSMA-I&T [ 75 , 81 , 98 , 123 – 126 ] (Annex Table- 5 ). The technical aspects of the respective studies have recently been summarized in a systematic review [ 127 ]. A comparative retrospective analysis, evaluating both radiopharmaceuticals with identical methods, confirmed the similarity of [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I&T regarding organs at risk [ 2 ] but has the limitation of low patient numbers and retrospective matched-pair analysis.…”

A Treatment Paradigm Shift: Targeted Radionuclide Therapies for Metastatic Castrate Resistant Prostate Cancer

“…Radiation safety precautions may be modeled after 177 Lu-DOTATATE therapy for neuroendocrine tumors given a shared radionuclide [ 26 , 34 ]. A recent meta-analysis of 177 Lu PSMA-617 dosimetry found that the lacrimal and salivary glands are the critical organs with the kidneys also receiving a significant radiation dose [ 35 ]. The calculated radiation absorbed doses to the lacrimal and salivary glands after 4 cycles of 177 Lu PSMA-617 is near the tolerated dose limit whereas the dose to the kidneys is far below the dose tolerance limits.…”