Abstract
1228
Objectives Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) is widely used in the assessment of coronary artery disease (CAD). We have developed 123I-CMICE-013 based on rotenone as a promising novel MPI agent. Our synthesis results in a mixture of 4 species of 123I-CMICE-013 designated as A (6%), B (6%), C (14%), D (74%). In this study, we collected NMR data to confirm their molecular structures, isolated the four 123I labeled tracers and performed microSPECT imaging and biodistribution studies.
Methods 123/127I-CMICE-013 was synthesized by reacting rotenone with Na123/127I in TFA with iodogen as the oxidizing agent at 60 °C for 45 min, and the four species were separated by RP-HPLC. MicroSPECT imaging and biodistribution studies were carried out on normal rats.
Results NMR confirmed the formation of C6’-I, C7’-OH bonds for diastereomeric pair A and B; and C6’-OH, C7’-I bonds for diastereomeric pair C and D. MicroSPECT images of 123I-CMICE-013 A, B, C, D in rats showed clear visualization of myocardium. Both imaging time activity curves (TAC) and biodistribution data showed that the heart uptake of B was significantly lower than A, C and D at all time points, while A, C, D were not statistically different. TAC showed that the liver uptake of the four tracers was not statistically different, except the uptake between B and C; and the heart to liver ratios did not indicate significant differences. The four isomers showed complex biodistribution profiles, which is not expected from the structure activity relationship theory.
Conclusions 123/127I-CMICE-013 A and B are constitutional isomers with C and D, while A and C are diastereomers of B and D, respectively. Since A, C and D have better imaging characteristics and represent ~95% of the product in the initial preparation, patient imaging studies with the mixture would be reasonable and simplify the manufacturing process.
Research Support CIHR/NSERC grant # RMIPJ 389641-09