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Interspecies Variation in Biodistribution of Technetium (2-Carbomethoxy-2-Isocyanopropane)₆⁺

The Joint Program in Nuclear Medicine, Harvard Medical School, and Brigham and Women's Hospital, Department of Radiology, Boston, Massachusetts
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts

Correspondence: For reprints contact: James F. Kronauge, PhD, Brigham and Women's Hospital, Department of Radiology, 75 Francis St., Boston, MA 02115.

ABSTRACT

The cationic complex technetium (2-carbomethoxy-2-isocyanopropane)₆^6> (^99mTc-CPI) contains terminal ester groups that were included to provide a pathway for in-vivo metabolism of this compound, thereby enhancing its performance as a myocardial perfusion agent. Biodistribution studies of the compound demonstrated myocardial accumulation in rabbit, guinea pig, and chick, but not in rat and mouse. Radiochemical analysis by HPLC after in-vitro incubation of ^99mTc-CPI in blood plasma from the various species confirmed enzymatic hydrolysis to numerous new compounds. Rat and mouse serum produced complete hydrolysis of this agent after incubation for less than 5 sec at 25°C or rates greater than 500 times those observed in human, rabbit, guinea pig and chick serum. Chemical synthesis and isolation of themonohydrolyzed species with subsequent biodistribution studies in guinea pig and rabbit confirmed that this neutral lipophilic complex did not accumulate in heart tissue. It is concluded that varying rates of enzymatic in-vivo hydrolysis produce the interspecies biodistribution differences and may account for the moderate myocardial clearance relative to other isonitrile complexes.