Radio therapy

The researches find that the Molecular Imaging (SNMMI) describes a new class of radiopharmaceuticals; named radiohybrids (rh), that offer a fresh perspective on cancer imaging and radioligand therapy (theranostics). In addition; the technology encompasses a highly innovative and efficient isotopic labelling method to facilitate broad application.

A new class of radiopharmaceuticals

“Similar to hybrid cars that are drive by either a combustion engine or an electric engine (one is switch on; while the other is switch off); They have design for the very first time radiopharmaceuticals with two ‘nuclear engines’ or isotopes;” explains Alexander Wurzer at Technical University Munich in Garching; Germany.

“For PET (positron emission tomography) imaging, the diagnostic isotope is radioactive (e.g., fluorine-18), while the therapeutic isotope is silent; for radiolig and therapy the situation is vice versa.” A unique feature of such rhPSMA-ligands is that both fluorine and the metal are always present; but only one of them is present as a radioactive isotope (e.g., [18F,natLu]rhPSMA or [19F,177Lu]rhPSMA).

The diagnostic isotope

“They have also create radiohybrids that offer a choice between two independent imaging isotopes; such as fluorine-18 (18F) or gallium-68 (68Ga), thus allowing for the optimal selection of the radioisotope by individual hospitals worldwide, in consideration of the local clinical infrastructure and isotope availability. Since these pairs of molecules are identical, they represent chemical monozygotic twins, which enables identical imaging with both of the chemical twins.”

Prostate cancer is the most commonly diagnose cancer among men in the United States, other than skin cancer. According to the American Cancer Society, approximately 175,000 new cases of prostate cancer are diagnose and more than 31,500 men die from the disease annually in the United States. For this study, prostate-specific membrane antigen (PSMA) is target. The researchers developed a platform technology that allows for fast and efficient labeling of peptide and peptide-like radiopharmaceuticals with either fluorine-18 (18F) or radiometals and then synthesized and evaluated several novel rhPSMA ligands.

Most promising candidates

Testing with six different rhPSMA ligands is carry out on prostate cancer tumor-bearing mice. Base on their high affinity, fast internalization and excellent biodistribution, the DOTA- and DOTAGA-derived inhibitors, rhPSMA-7 and 10, were found to be the most promising candidates for first in human proof-of-concept.

That proof-of-concept was performed using [18F,natGa]rhPSMA-7 PET imaging in a patient suffering from metastatic, castration-resistant prostate cancer. The results showed fast blood clearance, almost no activity transfer into the bladder during imaging; and the radiohybrid compound demonstrated high-contrast PET imaging of lymph nodes and bone metastasis.