The challenge of prostate cancer imaging is being tackled by a new radionuclide drug, which also acts as a cancer-killing therapy of tumors in and out of the prostate, new research suggests. The findings were presented recently at the 2015 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (6–10 June, Baltimore, MD, USA).
The new agent delivers diagnostic- or therapy-grade radionuclides to cells expressing a protein known as prostate-specific membrane antigen (PSMA). This protein is expressed on the surface of prostate cancer cells, as well as resulting metastatic cells throughout the body. Using a special hybrid scanner utilized to perform minimally invasive positron emission tomography, clinicians are able to diagnose and stage the disease, and monitor therapy.
Although still in its initial stages, the PMSA-inhibiting theranostic agent PSMA-617 could be used for the treatment of individuals with hormone-refractory prostate cancers, which are difficult to treat and associated with poor prognosis. These patients have few options and those they have come with substantial adverse effects.
PSMA-617 may allow more effective and sensitive visualization, better staging and significantly higher therapeutic potential. Although other-PMSA-based theranostics have reached the research stage, they have been associated with an excess of limitations such as instability in live subjects, lack of imaging contrast between tissue and background signal and increased binding to other organs such as the kidneys. PMSA-617 demonstrated strong binding to the target protein and is readily taken up by malignant PMSA-positive tumors. It is possible that the drug could represent a watershed moment in prostate cancer theranostics.
In order to study the effects of the compound, mice were imaged with an imaging-grade radionuclide, gallium-68, in order to examine the diagnostic value of PSMA-617. Then a therapy-grade radionuclide, lutetium-177, was administered – this delivers a more powerful dose of radiation, destroying the cells and tissues of tumors when combined with PMSA-617. A first-in-human clinical trial of both imaging and therapy in a single person was then carried out.
It was shown by the human study that imaging was effective for the evaluation of metastatic prostate cancer. A drop in prostate-specific antigen levels from 38.0 to 4.6 nanograms per millilitre was seen with subsequent therapy. Verification of response to therapy was carried out using combined positron emission tomography and computed tomography.
Statistics from the American Cancer Society show that approximately one out of seven men will be diagnosed with prostate cancer in their lifetime. In the US this year there are expected to be 220,800 new prostate cancer diagnoses and 27,540 prostate-cancer-related deaths.
“Prostate cancer still represents one of the main causes for cancer-related deaths among men,” commented co-author Matthias Eder from the German Cancer Research Center (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.”