Synthesis and biological evaluation of 99mTc-DHPM complex: a potential new radiopharmaceutical for lung imaging studies

In the recent years interests on dihydropyrimidinone and their analogues have increased potentially due to their wide range of pharmacological/biological activities. Synthesis, radiolabeling with technetium-99 m (Tc-99m) and biological evaluation of 5-etoxycarbonyl-4-phenyl-6-methyl-3,4-dihydro-(1H)-pyrimidine-2-one (DHPM) were studied in this present work. After synthesis complexation of DHPM with Tc-99m was carried out using stannous chloride as the reducing agent. The complex (Tc-99m-DHPM) was characterized by thin layer chromatography, radio-HPLC technique and determination of partition co-efficient. Radiochemical stability and particle size distribution of the complex were also measured. Biodistribution/scintigraphy studies were performed in rats and rabbits to evaluate the pharmacological characteristics of this complex. The radiochemical purity of the complex was over 95% as studied by thin layer chromatography and radio-HPLC. It was stable over 24 h at room temperature. Its partition coefficient indicated that it was a lipophilic complex. According to the European Pharmacopeia, > 80% of Tc-99m labeled radiopharmaceutical (Tc-99m-MAA) in the size range 10-50 mu m, must be accumulated in the lungs 15 min after intravenous administration. In this study > 85% of the Tc-99m-DHPM complex in the average size of 40 mu m. Biodistribution studies of Tc-99m-DHPM in rat revealed that the complex accumulated in the lung with high uptake and good retention after intravenous administration. Scintigraphic studies in rabbit also revealed that most of the administered radiolabeled complex was accumulated in the lungs and after 1 h slowly excreted through the renal system. The lung uptake (ID%/g) was 10.12, 9.67, 8.60 and 5.01 and the lung/liver ratio was 7.49, 2.88, 2.62 and 1.87 at 2, 15, 30 and 60 min post-injection, respectively. These results suggested that Tc-99m-DHPM could be suitable as a potential lung perfusion imaging agent. Further studies with Tc-99m-DHPM and its derivatives are warranted to develop new Tc-99m-labeled imaging agents for clinical applications.