Gallium-68 PSMA-617

In solid tumors, there are multiple barriers for a chimeric antigen receptor (CAR) T cell to surmount in order to reach the tumor site. For better understanding whether CAR T cells effectively infiltrate into tumor site, and simultaneously, whether there are off-target effects, real-time monitoring technologies need to be established. Cell-based positron emission tomography reporter genes have been developed to monitor engineered cells in living subjects. In this study, we reported the construction of a novel reporter gene truncated prostate-specific membrane antigen (ΔPSMA) pending for monitoring CAR T cells using 68Ga-PSMA-617 and a method for tracking the distribution of CAR T cells in vivo was developed. Data were provided to demonstrate that ΔPSMA was predominantly localized on the plasma membrane and could take up 68Ga-PSMA-617 in vitro in a time-dependent manner. And the expression of ΔPSMA did not affect CAR expression and cytolytic capacity of CAR T cells. CAR-ΔPSMA T cell xenografts in nude mice were clearly imaged by positron emission tomography 60 min after injection of 68Ga-PSMA-617. PSMA paired with 68Ga-PSMA-617 was capable of identifying approximately 1 × 104 engineered CAR T cells. The ability to image small numbers of CAR T cells in vivo would be helpful to accelerate the translation of cell-based therapies into the clinic, and it may reinforce our understanding of treatment success, failure, and toxicity.

Prostate-specific membrane antigen (PSMA)-based PET/CT imaging has limitations in the diagnosis of prostate cancer (PCa). We recruited 207 participants with suspicious PCa to perform PET/CT imaging with radiolabeled gastrin-releasing peptide receptor (GRPR) antagonist, [⁶⁸Ga]Ga-RM26, and compare with [⁶⁸Ga]Ga-PSMA-617 and histopathology.

Every participant with suspicious PCa was scanned with both [⁶⁸Ga]Ga-RM26 and [⁶⁸Ga]Ga-PSMA-617 PET/CT. PET/CT imaging was compared using pathologic specimens as a reference standard.

Of the 207 participants analyzed, 125 had cancer, and 82 were diagnosed with benign prostatic hyperplasia (BPH). The sensitivity and specificity of [⁶⁸Ga]Ga-RM26 and [⁶⁸Ga]Ga-PSMA-617 PET/CT imaging differed significantly for detecting clinically significant PCa. The area under the ROC curve (AUC) was 0.54 for [⁶⁸Ga]Ga-RM26 PET/CT and 0.91 for [⁶⁸Ga]Ga-PSMA-617 PET/CT in detecting PCa. For clinically significant PCa imaging, the AUCs were 0.51 vs. 0.93, respectively. [⁶⁸Ga]Ga-RM26 PET/CT imaging had higher sensitivity for PCa with Gleason score (GS) = 6 (p = 0.03) than [⁶⁸Ga]Ga-PSMA-617 PET/CT but poor specificity (20.73%). In the group with PSA < 10 ng/mL, the sensitivity, specificity, and AUC of [⁶⁸Ga]Ga-RM26 PET/CT were lower than [⁶⁸Ga]Ga-PSMA-617 PET/CT (60.00% vs. 80.30%, p = 0.12, 23.26% vs. 88.37%, p = 0.000, and 0.524 vs. 0.822, p = 0.000, respectively). [⁶⁸Ga]Ga-RM26 PET/CT exhibited significantly higher SUVmax in specimens with GS = 6 (p = 0.04) and in the low-risk group (p = 0.01), and its uptake did not increase with PSA level, GS, or clinical stage.

This prospective study provided evidence for the superior accuracy of [⁶⁸Ga]Ga-PSMA-617 PET/CT over [⁶⁸Ga]Ga-RM26 PET/CT in detecting more clinically significant PCa. [⁶⁸Ga]Ga-RM26 PET/CT showed an advantage for imaging low-risk PCa.