Positron Emission Tomography/Computed Tomography with Gallium-68–labeled Prostate-specific Membrane Antigen Detects Relapse After Vascular-targeted Photodynamic Therapy in a Prostate Cancer Model

Abstract

BackgroundEvaluating the efficacy of focal therapy for prostate cancer is limited by current approaches and may be improved with biological imaging techniques. ObjectiveWe assessed whether positron emission tomography/computed tomography with gallium-68–labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) can be used to predict relapse after vascular-targeted photodynamic therapy (VTP). Design, setting, and participantsA total of 1×106 LNCaP cells were grafted subcutaneously in the flanks of 6–8–wk-old SCID mice. Of 24 mice with measurable tumors 6 wk after tumor implantation, 20 were treated with VTP (150mW/cm2) to ablate the tumors. Blood prostate-specific antigen (PSA) levels were assessed, and ⁶⁸Ga-PSMA PET/CT images were performed 1 d before VTP and 1 and 4 wk after. Outcome measurements and statistical analysisLocal tumor relapse was evaluated by histology, and tumors were analyzed by prostate-specific membrane antigen (PSMA) and PSA immunohistochemistry. T tests and Kruskal-Wallis tests were used to determine significance. Results and limitationsFour weeks after VTP, 11 (65%) mice had complete responses and six (35%) had tumor relapses confirmed by histology (hematoxylin and eosin, and PSMA immunohistochemistry). All mice with local relapse had positive 68Ga-PSMA PET/CT findings 4 wk after VTP; all complete responders did not. One week after VTP, the relapse detection sensitivity of 68Ga-PSMA PET/CT was 75%, whereas the sensitivity of PSA was only 33%. Compared with controls, relapsed tumors had a three-fold reduction in the number of cells with strong PSA staining by immunohistochemistry (1.5% vs 4.5%; p=0.01). ConclusionsIn a preclinical prostate cancer model, we show that 68Ga-PSMA PET/CT can identify and predict relapse earlier than blood PSA level. These findings support further testing in clinical trials. Patient summaryPositron emission tomography/computed tomography with gallium-68–labeled prostate-specific membrane antigen may be used to follow and evaluate treatment outcomes in men who receive focal therapy for prostate cancer.