Evaluation of [68Ga]DOTA-IR-780-C-4 in PET Imaging Studies for PSMA-Positive Prostate Cancer Patients

• Status: ENROLLING_BY_INVITATION
• Trial end date: 2026-12-16

Summary

Prostate cancer is one of the most common malignant tumors in the urinary and male reproductive systems. According to the 2020 edition of the Global Cancer Statistics Report published by the WHO International Agency for Research on Cancer in February 2021, newly diagnosed prostate cancer cases worldwide accounted for 7.3% of all malignant tumors in 2020, with an incidence rate ranking third after breast cancer and lung cancer. Deaths from prostate cancer accounted for 3.8% of all malignant tumor deaths, ranking eighth. In January 2019, the National Cancer Center released the latest incidence and mortality data of malignant tumors in China in 2015. Among them, there were 72,000 new prostate cancer cases, with an incidence rate of 10.23 per 100,000, ranking sixth among male malignant tumors; 31,000 deaths, with a mortality rate of 4.36 per 100,000, ranking tenth among male malignant tumors. Compared with European and American countries, prostate cancer in China has a relatively high mortality rate, mainly because most patients are diagnosed at an advanced stage. "Early diagnosis and early treatment" are important means to prolong the survival period and reduce the mortality rate of prostate cancer patients. Currently, the diagnostic methods for prostate cancer mainly include digital rectal examination, tumor markers, imaging examinations, and prostate biopsy.

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein secreted by prostate epithelial cells, which is highly expressed in the cell membrane of prostate cancer cells and their metastases. PSMA is also weakly expressed in normal tissues such as the small intestine, brain, kidneys (proximal convoluted tubules), duodenal mucosa, parotid gland, and submandibular gland, but only at 1/1000 to 1/100 of the level in prostate cancer. Bostwick et al. used the PSMA-targeting antibody 7E11-C5 to detect tissues from 184 patients with prostate cancer lesions and found that the staining intensity was higher in prostate cancer tissues with higher Gleason scores. Subsequent studies by Silver et al. also found that the expression level of PSMA in prostate cancer tissues is much higher than that in normal prostate tissues, and its expression level is significantly correlated with the pathological stage of prostate cancer, with an expression rate of up to 96%-98% in lymph node metastases. The specific high expression of PSMA in cancer tissues makes it an important target for the diagnosis and treatment of prostate cancer, and a large number of radioactive molecular probes have been developed targeting this target for the diagnosis of prostate cancer, showing good target affinity.

The properties of different PSMA radiotracers vary slightly. Inhibitors of PSMA are mainly divided into three categories: phosphorous-based, thiol-based, and urea-based. Among them, the most widely used PSMA PET imaging agents are urea-based small molecules, such as 68Ga-PSMA-11, 68Ga-PSMA-617, 68Ga-PSMA-I\&T, 18F-DCFBC, 18F-DCFPyL, and 18F-PSMA-1007. Multiple studies have shown that compared with other PET imaging modalities or traditional imaging, PSMA PET imaging has significant advantages, including higher specificity, sensitivity, and positive predictive value.

68Ga-labeled PSMA ligands, as the first PSMA PET imaging agents applied to prostate cancer, have shown promising prospects in tumor localization, local staging, detection of biochemical recurrence (BCR), metastasis detection, and guiding treatment. Among these ligands, PSMA-11 is the most clinically used. 68Ga-PSMA-11 was approved by the FDA in December 2020. It is very helpful for prostate cancer patients with suspected metastasis or recurrence. For suspected metastases and recurrence, it can specifically bind to PSMA, clearly visualize lesions in PET imaging, accurately detect potential foci, provide important diagnostic basis for clinical practice, and assist doctors in judging disease progression and formulating effective treatment plans.

Another similar product, Pluvicto, was approved by the FDA in March 2022. It is used for patients with suspected metastatic prostate cancer scheduled for initial radical treatment, patients with suspected recurrent prostate cancer with elevated PSA levels, and screening metastatic prostate cancer patients eligible for 177Lu-PSMA-617 targeted therapy.

In summary, this product shares the same target and nuclide (68Ga) as Pluvicto, and is expected to have obvious diagnostic performance in PSMA-positive prostate cancer. The experimental results of Pluvicto have demonstrated acceptable safety and good effectiveness of the drug, thus ensuring the safety and effectiveness of this probe.

• Phase: NA

Details

• Lead Sponsor: Affiliated Hospital of Jiangnan University