Clinical Evaluation of Ultrasound-Enhanced Radiotracer Uptake for Radioligand Therapy in Metastatic Prostate Cancer

Abstract

Background:

Low-intensity pulsed ultrasound (LIPUS) may noninvasively enhance intratumoral delivery of radiopharmaceuticals, but clinical data are scarce. The authors prospectively evaluated whether adding LIPUS to prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) improves uptake and outcomes in metastatic prostate cancer while maintaining safety.

Methods:

A total of 42 men with PSMA PET-positive metastatic prostate cancer received up to six cycles of ¹⁷⁷Lu-PSMA-617. Before each infusion, LIPUS (1 MHz, 0.5–2.0 W/cm², 10 min) was applied to one dominant metastasis. Baseline and postcycle-1 PSMA PET/CT measured percent change in SUV_max (ΔSUV_max) for the sonicated lesion versus a matched nonsonicated reference lesion. Patients were classified as high (ΔSUV_max ≥20%) or low enhancement. Prostate-specific antigen (PSA) response, progression-free survival (PFS), and toxicity were recorded.

Results:

LIPUS was feasible in all patients without treatment interruptions. Sonicated lesions showed higher uptake (median ΔSUV_max + 32%) than reference lesions (+3%; p < 0.001). High-enhancement patients had more PSA_50 responses (71% vs. 33%) and longer PFS (11.5 vs. 5.3 months; hazard ratio 0.35). Adverse events were mainly Grades 1–2 local discomfort and typical ¹⁷⁷Lu-PSMA toxicities; no Grade ≥3 LIPUS-related events occurred.

Conclusions:

US-enhanced RLT appears safe and can increase intratumoral radiotracer uptake, translating into improved biochemical control and PFS in metastatic prostate cancer.