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Relative Uptake, Metabolism, and ß-Receptor Binding of (1R,2S)-4-¹⁸F-Fluorometaraminol and ¹²³I-MIBG in Normotensive and Spontaneously Hypertensive Rats

¹ Institut für Nuklearchemie Forschungszentrum Jülich, Jülich, Germany

The objective of the study was to compare relative uptake, metabolism, and ß-receptor affinity of the new positron-emitting uptake-1 tracer (1R,2S)-4-¹⁸F-fluorometaraminol (4-FM) with those of the SPECT pharmaceutical meta-¹²³I-iodobenzylguanidine (MIBG) in Wistar Kyoto (WKY) rats and spontaneously hypertensive (SHR) rats. Methods: No-carrier-added 4-¹⁸F-FM was applied to SHR and WKY rats in vivo and to retrogradely perfused hearts in vitro. Cardiac and extracardiac distribution was assessed, and metabolite formation was determined by thin-layer chromatography. The in vivo experiments were repeated with no-carrier-added ¹²³I-MIBG. By means of autoradiography, the ß-receptor affinity of 4-FM was compared with that of MIBG and propranolol (10 µmol/L) through displacement of ¹²⁵I-iodocyanopindolol (1.5 pmol/L) in slices of heart and spleen. Results: Cardiomyopathic hearts showed heterogeneous 4-¹⁸F-FM uptake with gradients up to 3.6 in vivo and in vitro between different regions of the heart. Control hearts showed such gradients in 4-¹⁸F-FM uptake only in vitro. ¹²³I-MIBG exhibited a less heterogeneous in vivo distribution in SHR hearts. Extracardiac differences between WKY and SHR were found for uptake of 4-¹⁸F-FM in the spleen (63.3% ± 4% vs. 38.8% ± 5.7% of cardiac activity) and for renal uptake of ¹²³I-MIBG (373% ± 27% vs. 81.4% ± 17% of cardiac activity). Metabolites of 4-¹⁸F-FM were found only in the liver and those of ¹²³I-MIBG were found in the liver and kidney with a nearly equal relative fraction in both types of animals of about 20%, 60%, and 30%, respectively. 4-FM suppressed cardiac-specific ß-receptor binding of ¹²⁵I-iodocyanopindolol in heart and spleen of both types of animals significantly, whereas MIBG had almost no effect. Conclusion: The more heterogeneous cardiac distribution of 4-¹⁸F-FM suggests that it reflects alterations in uptake-1 better than ¹²³I-MIBG in addition to the possibility of quantification and higher spatial resolution by PET compared with SPECT. Altered biotransformation in cardiomyopathic diseases may also impair the evaluation of ¹²³I-MIBG-SPECT data. The ß-receptor binding of 4-¹⁸F-FM must be further elucidated.

Key Words: ¹⁸F-fluorometaraminol • meta-¹²³I-iodobenzylguanidine • cardiomyopathy • ß-receptors • uptake-1