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

Minseok Suh; Hyun Gee Ryoo; Keon Wook Kang; Jae Min Jeong; Chang Wook Jeong; Cheol Kwak; Gi Jeong Cheon

doi:10.3348/kjr.2022.0176

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

Korean J Radiol. 2022 Sep;23(9):911-920. doi: 10.3348/kjr.2022.0176. Epub 2022 Jun 20.

Authors

Minseok Suh¹, Hyun Gee Ryoo^{1

2}, Keon Wook Kang^{1

3}, Jae Min Jeong¹, Chang Wook Jeong⁴, Cheol Kwak⁴, Gi Jeong Cheon^{1

5}

Affiliations

¹ Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
² Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
³ Cancer Research Institute, Seoul National University, Seoul, Korea.
⁴ Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
⁵ Cancer Research Institute, Seoul National University, Seoul, Korea. larrycheon@gmail.com.

Abstract

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.

Keywords: ⁶⁸Ga-NGUL; Dosimetry; PET/CT; PSMA; Prostate cancer.

Publication types

Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Gallium Radioisotopes
Healthy Volunteers
Humans
Male
Positron Emission Tomography Computed Tomography* / methods
Prospective Studies
Prostate / pathology
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / pathology

Substances

Gallium Radioisotopes