Cold Kit PSMA PET Imaging: Phase I study of ⁶⁸Ga-THP-PSMA PET/CT in patients with prostate cancer

Abstract

Objectives: Ga-68 labelled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as ⁶⁸Ga-HBED-PSMA-11, are promising small molecules for targeting prostate cancer. A new radiopharmaceutical ⁶⁸Ga-THP-PSMA has a simplified design for one-step kit-based radiolabelling. It features the tris(hydroxypyridinone) (THP) ligand, which complexes ⁶⁸Ga3+ rapidly at low concentration, room temperature and over a wide pH range, enabling direct elution from a ⁶⁸Ge/⁶⁸Ga generator into a lyophilized kit in one-step without manipulation. This Phase I study aimed to assess the safety and biodistribution of ⁶⁸Ga-THP-PSMA. Methods: Cohort A: 8 patients with proven prostate cancer scheduled to undergo prostatectomy underwent PET/CT following administration of ⁶⁸Ga-THP-PSMA (Gleason score 7-10; PSA mean 7.8, range 5.4-10.6). All patients proceeded to prostatectomy (7 with pelvic nodal dissection). Dosimetry was performed with OLINDA/EXM from multi-time point PET imaging. Cohort B: 6 patients with a positive ⁶⁸Ga-HBED-PSMA-11 PET/CT underwent comparative ⁶⁸Ga-THP-PSMA scan. All patients were followed to evaluate for adverse events. Results: No adverse events occurred. Cohort A: Six of 8 patients had focal uptake in the prostate (at 2 h, average SUV_max 5.1, range 2.4–9.2) with correlative 3+ staining on PSMA immunohistochemistry on prostatectomy specimens. The two ⁶⁸Ga-THP-PSMA negative scans had only 1+/2+ staining. The mean effective dose was 2.07E-02 mSv/MBq. Cohort B: ⁶⁸Ga-THP-PSMA had lower physiologic background uptake compared to ⁶⁸Ga-HBED-PSMA-11 (parotid: mean SUV_max 3.6 compared to 19.2, liver: 2.7 to 6.3, spleen 2.7 to 10.5, p<0.001 for all). In 5 of 6 patients there was concordance in the number of metastases identified with ⁶⁸Ga-HBED-PSMA-11 and ⁶⁸Ga-THP-PSMA. 13 of 15 nodal abnormalities were sub-centimetre. In 22 malignant lesions, tumor-to-liver contrast was similar on THP-PSMA compared to HBED-PSMA (4.7 to 5.4, P = 0.15) despite higher SUV_max with HBED-PSMA (30.3 to 10.7, p<0.01). Conclusion: ⁶⁸Ga-THP-PSMA is safe with favourable biodistribution for clinical imaging. Observed focal uptake in the prostate localized to PSMA-expressing malignant tissue on histopathology. Metastatic PSMA-avid foci are also visualized with ⁶⁸Ga-THP-PSMA PET. Single step production from a GMP cold kit may enable rapid adoption.