Development of glucose-based pure beta minus radiotracers potentially suitable for tumor radioguided surgery.
The radioguided surgery (RGS) is crucial for the survival of tumor patients when the cancer mass removal is the only therapeutic option. Recognized methods use gamma-emitting radiotracers, but their limit is the high penetration power of gamma rays. Since these latter can traverse large amounts of tissue any eventual uptake of the tracer by nearby healthy tissues would represent a non-negligible background that often prevents the technique's applicability. Recently, in order to overcome these limits, it has been proposed the use of pure beta- emitters. Indeed, the beta- radiation penetrates only a few millimeters of tissue, and this feature could be exploited intraoperatively because it reduces the amount of background radiation from healthy tissues around the lesion, allowing a smaller radiopharmaceutical absorbed dose to detect tumor remnants and the possibility to extend the RGS to cases with a large uptake from surrounding healthy organs. To date, the validation of beta- RGS strictly depends on the availability of tumor specific beta- radiotracers. Since for many tumors that would significantly profit from RGS are available only gamma/beta+ radioimaging agents, the idea to be developed in this project is to convert the most widely used beta+ radiopharmaceutical 2-[18F]Fluoro-2-Deoxy-Glucose (FDG) into new pure beta- tracers suitable for RGS by substituting its radioisotope with the beta- emitting radiometal 90Yttrium by the means of the bifunctional chelate (BFC) design approach. (Non)-conventional design, synthesis, and labeling methods will be applied for the preparation first of "cold" tracers (89Y-containing) to be evaluated for the chemical/serum stability and the uptake in human cancer cells expressing the specific transporters of glucose, and then for providing real radiotracers (90Y-containing) to be assayed for the selective uptake in cancer cells.