Radionuclide Drug Combines Prostate Imaging and Therapy
A novel radionuclide drug may combine prostate cancer imaging and cancer-killing therapy for tumors both in and out of the prostate, according to German researchers.

The drug delivers diagnostic- or therapy-grade radionuclides to cells that express a protein called prostate-specific membrane antigen (PSMA), found on the surface of prostate cancer cells and their metastatic counterparts throughout the body. Clinicians can diagnose or stage the disease and monitor therapy using PET/CT.

"Prostate cancer still represents one of the main causes for cancer-related deaths among men," says Matthias Eder, PhD, coauthor of the study and a researcher in the division of radiopharmaceutical chemistry at the German Cancer Research Center in Heidelberg, Germany. "The diagnosis and therapy of metastatic prostate cancer is still challenging. The current clinical methods are not sensitive enough for detecting disease beyond the prostate, but we are convinced that this novel theranostic radiotracer represents a significant step forward that could have a major impact on the future of prostate cancer care."

The PSMA-inhibiting agent, called PSMA-617, is still in its initial stages, but it could prove an ideal treatment for patients with hormone-refractory prostate cancers, which are notoriously difficult to control and linked to poor prognosis. Options for these patients are few, and they come with substantial adverse effects. Diagnosis and therapy with the theranostic agent PSMA-617 could offer more effective and sensitive visualization, better staging and significantly higher therapeutic potential.

 To be clear, other PSMA-based theranostics have reached the research bench, but previous contenders had too many limitations in terms of instability in live subjects, a lack of imaging contrast between targeted tissue and background signal, and increased PSMA-associated binding to normal organs such as the kidneys. This new radionuclide drug shows strong binding to the protein PSMA and is readily and safely taken up by malignant PSMA-positive tumors.

For this research, scientists first imaged mice with an imaging-grade radionuclide, gallium-68, to assess the diagnostic value of PSMA-617. Diagnostic imaging was followed by a therapy-grade radionuclide, lutetium-177, which delivers a more powerful dose of radiation that penetrates and destroys the cells and tissues of tumors when combined with PSMA-617. This phase was followed by a first-in-human clinical trial of both imaging and therapy in a single person.

Results of the human study showed that imaging was effective for the evaluation of metastatic prostate cancer, and subsequent therapy resulted in a drop in prostate-specific antigen levels from 38 to 4.6 ng/mL. Positive response to therapy was verified via PET/CT.