Phase I Clinical Trial of Prostate-Specific Membrane Antigen-Targeting 68Ga-NGUL PET/CT in Healthy Volunteers and Patients with Prostate Cancer

• Published in: Korean journal of radiology Vol. 23; no. 9; pp. 911 - 920
• Main Authors: Suh, Minseok, Hyun Gee Ryoo, Kang, Keon Wook, Jeong, Jae Min, Jeong, Chang Wook, Kwak, Cheol, Gi Jeong Cheon
• Format: Journal Article
• Language: English
• Published: Seoul The Korean Society of Radiology 01.09.2022; 대한영상의학회
• Subjects: Adults; Antigens; Biodistribution; Bladder; Blood; Cancer therapies; Clinical trials; Coronary vessels; Dosimetry; Drug dosages; Exocrine glands; FDA approval; Kinases; Liver; Medical imaging; Medical laboratories; Metastasis; Nuclear Medicine; Patients; Prostate cancer; Radiation; Scintigraphy; Spleen; 방사선과학
• ISSN: 1229-6929; 2005-8330; 2005-8330
• DOI: 10.3348/kjr.2022.0176

Objective 68Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N, N′, N″-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68Ga-NGUL in healthy volunteers and the lesion detection rate of 68Ga-NGUL in patients with prostate cancer. Materials and Methods We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68Ga-NGUL (2 MBq/kg; 96–165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results All 12 participants (six healthy adults aged 31–32 years and six prostate cancer patients aged 57–81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68Ga-NGUL PET/CT or conventional imaging. Among them, 68Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion 68Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68Ga-NGUL is a valuable option for prostate cancer imaging.