New thesis paving the way towards earlier diagnosis of prostate cancer

Every year, more than ten thousand Swedish men are diagnosed with prostate cancer, and despite gaining access to increasingly effective treatments, it is currently the form of cancer that causes the highest mortality rate in our country. One of healthcare’s greatest challenges is to make correct diagnosis already at an early stage in the course of the disease. Thus, the need for updated tools is urgent, and in a new thesis, Fanny Lundmark, PhD student at Uppsala University, is presenting new substances with the potential to enable painless and more effective diagnostics.

“The approaches available to clinics today exhibit poor accuracy and can be both painful and unpleasant for the patient. We have instead chosen to focus on radionuclide-based imaging, a technique offering several important advantages. Our work is based on the biomarkers PSMA and GRPR, which are overexpressed on the surface of prostate cancer cells, and we have now modified a number of molecules that bind to both biomarkers. Thereby enabling the possibility to visualise both primary tumors and the smallest metastases,” states Fanny Lundmark.

The substances Lundmark has developed – so-called radioligands – combine the molecule that binds to the biomarker with a radionuclide via a linker optimising the relationship between the two. The decay of the radionuclide is possible to detect with PET or SPECT, in turn generating images of the prostate cancer cells. One of the molecules presented in Lundmark’s thesis has already been tried in a clinical study, where it successfully visualised cancer cells without causing unwanted side effects.

“We have optimised PSMA- and GRPR-binding molecules separately before combining them into a single radioligand with the ability to bind to both biomarkers. This increases the chance of early and correct diagnosis, and our data indicate that this is indeed the case. We have also investigated different types of radioisotopes to enable imaging with PET, which offers several advantages in comparison with SPECT.”

The ambition with this technology is to replace today's need for physical palpation of the prostate, biosampling and rectal ultrasound with modern imaging technology. In parallel, the research group has already begun work to further modificate the radioligands, now aiming to also enable treatment of the tumor cells as the molecules bind to them.

“Using an isotope suitable for targeted radiation therapy, both metastases and tumors can be identified and irradiated with minimal impact on surrounding tissue. We see many interesting tracks to explore and improve, and in the long term we hope that our results will make valuable contributions to help all men affected by prostate cancer being spared incomplete diagnoses and surgical interventions, and above all to longer and better lives.”

text: Magnus Alsne, photo: Mikael Wallerstedt, Ottilia Andersson