title: Relative uptake, metabolism, and beta-receptor binding of (1R,2S)-4-(18)F-fluorometaraminol and (123)I-MIBG in normotensive and spontaneously hypertensive rats.
abstract: The objective of the study was to compare relative uptake, metabolism, and beta-receptor affinity of the new positron-emitting uptake-1 tracer (1R,2S)-4-(18)F-fluorometaraminol (4-FM) with those of the SPECT pharmaceutical meta-(123)I-iodobenzylguanidine (MIBG) in Wistar Kyoto (WKY) rats and spontaneously hypertensive (SHR) rats.
  
  
  METHODS
  No-carrier-added 4-(18)F-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 (123)I-MIBG. By means of autoradiography, the beta-receptor affinity of 4-FM was compared with that of MIBG and propranolol (10 micromol/L) through displacement of (125)I-iodocyanopindolol (1.5 pmol/L) in slices of heart and spleen.
  
  
  RESULTS
  Cardiomyopathic hearts showed heterogeneous 4-(18)F-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-(18)F-FM uptake only in vitro. (123)I-MIBG exhibited a less heterogeneous in vivo distribution in SHR hearts. Extracardiac differences between WKY and SHR were found for uptake of 4-(18)F-FM in the spleen (63.3% plus minus 4% vs. 38.8% plus minus 5.7% of cardiac activity) and for renal uptake of (123)I-MIBG (373% plus minus 27% vs. 81.4% plus minus 17% of cardiac activity). Metabolites of 4-(18)F-FM were found only in the liver and those of (123)I-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 beta-receptor binding of (125)I-iodocyanopindolol in heart and spleen of both types of animals significantly, whereas MIBG had almost no effect.
  
  
  CONCLUSIONS
  The more heterogeneous cardiac distribution of 4-(18)F-FM suggests that it reflects alterations in uptake-1 better than (123)I-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 (123)I-MIBG-SPECT data. The beta-receptor binding of 4-(18)F-FM must be further elucidated.
authors.affiliation: Institut für Nuklearchemie Forschungszentrum Jülich, Jülich, Germany. m.pissarek@fz-juelich.de
authors.forename: Margit
authors.initials: M
authors.lastname: Pissarek
authors.forename: Johannes
authors.initials: J
authors.lastname: Ermert
authors.forename: Guido
authors.initials: G
authors.lastname: Oesterreich
authors.forename: Dirk
authors.initials: D
authors.lastname: Bier
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Coenen
mesh_terms: D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D009202:Cardiomyopathies / Q000000981:diagnostic imaging; D006321:Heart / Q000000981:diagnostic imaging*; D006973:Hypertension / Q000000981:diagnostic imaging* / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D020120:Iodocyanopindolol / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008680:Metaraminol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D009206:Myocardium / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C413488:4-fluorometaraminol; D000319:Adrenergic beta-Antagonists; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta; D019797:3-Iodobenzylguanidine; D008680:Metaraminol; D020120:Iodocyanopindolol; D011433:Propranolol