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

Abstract

Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

PSMA Radioligand Therapy in Prostate Cancer

“…Regarding mCRPC, PSMA-RLT is evidence category 1A in advanced-stage mCRPC patients 8,82,83 . The refinement of a single-treatment strategy is one of the main targets in this population.…”

“…BRCA1 and BRCA2 mutations are predictive for treatment response with olaparib monotherapy or a combined PARPi/ARTA approach. For patients after at least one treatment line of ARTA and one line of chemotherapy, 177 Lu-PSMA-617 appears as an evidence category 1 in patients with PSMA-positive metastases 2–5,8 …”

“…Life expectancy and risk of death due to prostate cancer should be considered when managing these patients 1,2,4,5 . A multidisciplinary approach is needed to ensure the best possible therapeutic strategies that may include observation, active surveillance, radical prostatectomy, radiation therapy, androgen deprivation therapy (ADT), chemotherapy, novel androgen receptor–targeted agents (ARTAs), polyadenosine diphosphate ribose polymerase inhibitor (PARPi), or radioligand therapy (RLT) with bone or prostate-specific membrane antigen (PSMA) agents 1,2,4,5,8 …”

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy

“…Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a cell-surface enzyme overexpressed on prostate cancer cells, making it an excellent target for PSMA-targeted diagnostic and therapeutic agents. Indeed, its potential for diagnosis and radionuclide treatment of prostate cancer has been demonstrated and well-reviewed. − Recently, FDA has approved [ 68 Ga]­Ga-PSMA-11 (Ga68 gozetotide), − [ 18 F]­DCFPyL (PYLARIFY, piflufolastat F18) − and [ 18 F]-rhPSMA-7.3 (POSLUMA, flotufolastat F 18) , for diagnostic imaging. PSMA PET scans are now being considered as a routine clinical procedure by urologists and oncologists for the diagnosis of prostate cancer.…”

“…PSMA PET scans are now being considered as a routine clinical procedure by urologists and oncologists for the diagnosis of prostate cancer. Additionally, FDA has approved [ 177 Lu]­Lu-PSMA-617 (Pluvicto, lutetium Lu-177 vipivotide tetraxetan) for radionuclide therapy. ,,, Another PSMA-targeting radionuclide therapy agent [ 177 Lu]­Lu-PSMA I&T is currently under phase III clinical trials. Many recent reports support using these Lu-177 agents for the treatment of prostate cancer patients. − …”