Study of the radiolabeling of substance P with Lutetium-177 and analysis of the stability in vitro: development of new radiopharmaceutical for tumor treatment

Substance P (SP) is an 11- amino acid neuropeptide, which is known as an important member of the family of the tachykinins, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH2. Radiolabeled SP has been described and proposal for detection and treatment of diseases such as arthritis and tumors. SP is the most important target of neurokinin 1 (NK-1) receptors, over expressed in malignant gliomas. 177Lu is commonly used in the production of radiopharmaceuticals for treatment of neuroendocrine tumors and is a radionuclide with favorable properties for endo radiotherapy. The half-life of 177Lu is 6.75 days and it emits b- particles of 497 keV average energy. Moreover, 177Lu also emits g radiation of 208 keV average energy, which makes imaging diagnosis possible. There are few studies describing radiolabeled SP analogs in literature and the objective of this work was to study the radiolabeling conditions and the stability of SP complexed to DOTA chelator, using 177Lu as radionuclide, in order to determine the best radiolabeling methodology. A high radiochemical purity (> 95%) and high specific activity of DOTA-SP was achieved when the reaction time was 30 minutes, the temperature was 90 deg C, the mass of DOTA-SP was 10 mg and 177Lu activity was 185 MBq. These conditions extrapolate will be used in future experiments with high activity and also in in vitro and in vivo studies involving glioma models. (author)