An easy-to-produce, low-cost, prostate cancer tracer has been developed by King’s College London PhD student Jennifer Young. Known as 68Ga-THP-PSMA, the new tracer, which was devloped with support from the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, can be made very quickly and easily in a radio-pharmacy, meaning that smaller hospitals and clinics can produce it. It is hoped that this will mean more patients will have access to high-quality lifesaving scans.
Tracers are radioactive dyes that are introduced, by injection or in liquid form, into a patient’s body before they have a positron emission tomography (PET) scan. As the tracer works its way around the body, organs and tissues affected by diseases such as cancer may absorb a higher or lower amount of the tracer than healthy tissues. The level of absorption can be detected by the scan and help specialists to detect disease.
Professor Philip Blower, from King’s School of Biomedical Engineering and Imaging Sciences, supervised Jennifer Young’s work with Dr Greg Mullen from radio-pharmaceutical company Theragnostics. He said: “The tracer Jennifer has developed will give more patients access to potentially lifesaving scans. The low-cost and relatively straightforward production process means that smaller hospitals and not just the biggest specialist hospitals can produce it for their patients.
“We hope this will be the first of several tracers based on this technology for application to other cancers, not just prostate.”
Only men have a prostate gland, its main job is to secrete fluid that nourishes and protects sperm. Prostate cancer is the most common cancer in men and there are currently more than 330,000 people living with the disease in the UK alone.
Greg Mullen, CEO of Theragnostics, said: “We are proud to present the results of this Phase I study alongside our colleagues at the trial’s sponsor the Peter MacCallum Cancer Centre, and King’s College London.
“These data demonstrate the disruptive technology of 68Ga-THP-PSMA, by simplifying and speeding up current production, while providing increased imaging sensitivity to support the discovery of prostate cancer.
“We are rapidly moving forward with the clinical development of 68Ga-THP-PSMA, and working with regulatory bodies to address an unmet clinical need by bringing this technology to prostate cancer patients.”
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 SUVmax 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 SUVmax 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 SUVmax 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.
Michael S Hofman, Peter Eu, Price Jackson, Emily Hong, David Binns, Amir Iravani, Declan Murphy, Catherine Mitchell, Shankar Siva, Rodney J Hicks, Jennifer D Young, Philip Blower, Gregory E Mullen