Phosphonate moiety: labeling with /sup 99m/Tc(Sn) after synthetic attachment to diverse biological compounds

The possibility of using the phosphonate moiety as a carrier of /sup 99m/Tc(Sn) while chemically attached to a compound possessing different biological properties was realized when 3-amino-3-carboxypropylphosphonic acid (ACPA) was synthesized. The nonphosphonate portion of the molecule was chosen because of its chemical similarity to the alpha-aminocarboxyl group of an amino acid. It was theorized that if the biokinetic properties of /sup 99m/Tc(Sn)ACPA were determined by the aminocarboxyl portion of the molecule rather than the phosphonate moiety, the compound might concentrate in areas of increased amino acid turnover. In general, however, its ultimate biological distribution could be a function of the following: The site of /sup 99m/Tc(Sn) binding on the ACPA molecule; the effectiveness with which the aminocarboxyl portion of the compound dominates biodistribution. The first was investigated by measuring the sequestration of insoluble tin hydroxide at pH 7.0 by several phosphonate compounds. The sequestration index of ACPA was comparable to that for diphosphonate (HEDSPA) and monophosphonate (hydroxylmethylphosphonic acid). The same study demonstrated that an amino acid, alanine, did not solubilize tin hydroxide (S.I. = 0). The data suggest that the phosphonate portion of the ACPA molecule binds the /sup 99m/Tc(Sn) but not the aminocarboxyl portion