A novel prostate-specific membrane antigen (PSMA)-targeted radioligand therapy shows the potential to enhance therapeutic effects for patients with PSMA-positive prostate cancer while eliminating the potential for severe adverse effects such as xerostomia, according to preclinical findings published in Molecular Imaging and Biology.
“Our study introduced a new PSMA-targeting ligand or molecule we call PSMA-1-DOTA with more favorable binding characteristics than existing treatments,” said lead study author Xinning Wang, PhD, Research Associate Professor in the Department of Biomedical Engineering and Member of the Cancer Imaging Program at the Case Comprehensive Cancer Center.
“This breakthrough could fundamentally change prostate cancer care by transforming PSMA-targeted therapy from a ‘last resort’ option to an earlier intervention,” said co-corresponding study author Zhenghong Lee, PhD, Professor in the Department of Radiology and Co-leader of the Cancer Imaging Program at the Case Comprehensive Cancer Center.
Background and Study Methods
Although PSMA-targeted radioligand therapy has been effective for treating patients with end-stage prostate cancer, the severe salivary gland toxicity caused by alpha emissions has led some patients to reject this treatment option or end treatment earlier. Limited success has been seen to date with various approaches tested for mitigating this toxicity.
Wang et al researched a new PSMA-targeting ligand, PSMA-1-DOTA, and explored its binding affinity and therapeutic effects in comparison with the radioligand therapies gallium Ga-68–labeled PSMA-11 (GaPSMA-11), Ga-68–labeled PSMA I&T (GaPSMA I&T), and lutetium Lu-177–labeled PSMA-617 (LuPSMA-617), in xenograft mouse models.
Additionally, a compassionate use study explored the use of positron-emission tomography (PET) imaging with Ga-68–labeled PSMA-1-DOTA (GaPSMA-1-DOTA) in a patient with metastatic castration-resistant prostate cancer who was treated at the Technical University of Munich in Germany.
Key Findings
PSMA-1-DOTA was found to have a fourfold higher binding affinity to PSMA compared with the other PSMA-targeted ligands. GaPSMA-1-DOTA demonstrated significantly lower kidney uptake and minimal salivary and lacrimal gland uptake on microPET/computed tomography (CT) imaging compared with other radioligands.
In the xenograft mouse models, LuPSMA-1-DOTA stopped tumor growth with efficacy similar to LuPSMA-617, “suggesting its potential to enhance the therapeutic window of targeted radioligand therapy by avoiding damage to the salivary glands,” the study authors noted.
In the compassionate use study, the patient had reduced uptake of GaPSMA-1-DOTA in the salivary glands.
The researchers are preparing a clinical trial for late next year for about 12 patients with prostate cancer to validate these results.
DISCLOSURE: For full disclosures of the study authors, visit link.springer.com.
