Practical Guide to 177Lutetium PSMA Peptide Receptor Radionuclide Therapy for Prostate Cancer

Introduction: Lutetium 177 (¹⁷⁷Lu) prostate-specific membrane antigen (PSMA) peptide receptor radionuclide therapy (PRRT) is an effective treatment for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor and taxane-based chemotherapy. It was recently approved by the U.S. Food and Drug Administration after its efficacy was demonstrated in the VISION trial. This education exhibit presents the clinical considerations and workflow involved in successful delivery of ¹⁷⁷Lu PSMA PRRT.

Methods: As with other radionuclide therapies, treating patients require the collaboration of a dedicated multidisciplinary team involving nuclear radiologists, oncologists, surgeons, and support staffs. An initial order is placed by medical oncologists after there is evidence of tumor progression detected by targeted PSMA PET imaging either with gallium 68 (⁶⁸Ga)-PSMA-11 or ¹⁸F-DCFPyL (2-(3-{1-carboxy-5-[(6-¹⁸F-fluoro-pyridine-3-carbonyl)- amino]-pentyl}-ureido)-pentanedioic acid) PSMA. The biodistribution of PSMA and the molecular imaging PSMA (miPSMA) expression score are shown.

Results: A nuclear radiologist uses a systematic list to ensure appropriateness of treatment, patient safety, and radiation safety. The patient chart and imaging are first reviewed to evaluate for any necessary additional consultation and tests. For example, metastasis that may benefit from local intervention needs to be evaluated by specialists, the patient’s functional status is considered, and certain lab thresholds must be met. After receiving a comprehensive evaluation, which may involve a review by the Prostate Theranostic Tumor Board, patients are scheduled for a consultation visit with the referring provider and a nuclear radiologist where the therapy is offered, safety information discussed, and informed consent received.

The ¹⁷⁷Lu PSMA PRRT therapy consists up to 6 cycles each separated by 6 weeks. ⁷⁷Lu is generated from a nuclear reactor, shipped through the airport to the hospital, and administered to the patient on the same day as delivery. Prior to each therapy session, the patient meets with the referring provider, a nuclear radiologist, and a nurse. Key lab values and adverse effects are monitored at each visit. ¹⁷⁷Lu PSMA PRRT is administered intravenously with a plan of mitigating immediate adverse effects. Patients may receive empiric dosing (6.0 or 7.4 GBq) adjusted for renal function or dosimetry-based dosing.

Conclusions: Whole body scan is performed 24-48 hours post-injection to confirm tumoral uptake, and SPECT/CT can be added to perform tumor and organ-specific dosimetry. Prior to the 3^rd and 5^th cycle, decision is made whether to continue therapy, which often involve assessing response to treatment by imaging. We routinely perform ⁶⁸Ga-PSMA-11 PET after 3^rd and 6^th cycles. Patients maintain clinical follow up with the referring provider 2-4 weeks post-therapy. Additionally in this exhibit, radiation safety instructions, adverse effects, and limitations are reviewed. Multiple patient scenarios are illustrated through case examples.