Evaluation of radioiodinated medium chain fatty acids as new diagnostic agents for the determination of hepatic viability

Radiopharmaceuticals which reflect beta-oxidation in hepatocytes will provi de useful information on the prognosis after surgery or on the efficacy of treatment, since beta-oxidation is the main pathway responsible for adenosi ne triphosphate in hepatocytes. We have previously developed [I-C-11]octano ate as a diagnostic agent for determination of hepatic viability by means o f positron emission tomography (PET), The goal of the present study was to develop a new radiopharmaceutical for single-photon emission tomography (SP ET), which has the advantage of being more widely used than PET. To this en d, two radioiodinated omega-(4-iodophenyl)-medium chain fatty acids, p-iodo phenylvaleric acid (IPVA) and p-iodophenylenanthic acid (IPEA), were synthe sized and evaluated as radiopharmaceuticals for determination of hepatic vi ability. Metabolite analyses in vitro and in vivo and a biodistribution stu dy in normal mice indicated that both compounds were taken up by the liver actively and metabolized by beta-oxidation. However, these studies also ind icated that IPEA is more suitable as an imaging agent than IPVA. Based on t hese results, SPET imaging studies were performed in normal and hepatitis m odel rats using [I-123]IPEA. The time-activity curves of the liver showed t wo-phase clearance of radioactivity in both normal and hepatitis model rats , but the clearance was delayed depending on the severity of hepatitis. Fur thermore, the clearance rate of the first phase was correlated with the ATP level in hepatocytes, which was used as an index of the energy production capacity of hepatocytes. In conclusion, IPEA was metabolized predominantly by beta-oxidation, and the clearance of IPEA from the liver was closely ass ociated with the ATP concentration in the liver. Thus, [I-123]IPEA is a pot entially useful new radiopharmaceutical for diagnosis of hepatic viability based on energy metabolism.