Tc-99m Labeled hexamethylenepropyleneamineoxime ([99mTc]-HMPAO) is a famous amine-oxime compound and is widely used to construct SPECT images of cerebral blood flow. To investigate the relationship between chemical structure and radiolabeling in
these
kind of diamine-oxime compounds, we synthesized seven compounds by Schiff's base formation and successive reduction with sodium borohydride. They were (RR/SS)-4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime (2),
(RR/SS/meso)-4,8-diaza-3,9-dimethy-lundecane-2,10-dione bisoxime (4), (RR/SS/meso) -4,8-diaza-3,10-dimethyldodecane-2.11-dione bisoxime(6), (RR/SS/meso)-4,7-diaza-3,6,6,8-tetramethyldecane-2,9-dione bisoxime(8),
(RR/SS/meso)-4,7-diaza-5.6-cyclohexy1-3,8-dimethyldecane-2,9-dione bisoxime (10), (RR/SS/meso)-3,4-bis(1-aza-2-methyl-3-oxime-1-butyl)-benzoic acid (12), and (RR/SS/meso)-2,3-bis(1-aza-2-methyl-3-oxime-1-butyl) benzophenone (14). Chemical
structures of
all the synthesized compounds were identified by taking 1H spectrum. Among them, 2 and 4 are propyleneamine oxime (PnAO), 6 is butyleneamine oxime (BnAO) and 8, 10, 12 and 14 are ethyleneamine oxime (EnAO). Each compound (0.5 mg) was incubated
with
stannous chloride (0.5g-8g), carbonate-bicarbonate buffer (final concentration = 0.1 M, pH 10) and Tc-99m-pertechenate (1 ml). Tc-99m labeling of these compounds were checked by ITLC (acetone), ITLC (normal saline), reverse phase TLC(50%
acetonitrile)
and ITLC (ethyl acetate). According to the results, EnAO's were not labeled by Tc-99m in any of above condition. About 11% of maximum labeling efficiency was obtained with BnAO. However, 4 (PnAO) was labeled with Tc-99m to 85 % which is similar
to
the
labeling efficiency of 2 (HMPAO). Hydrophilic impurity (9%) was the most significant problem with the labeling of 4, however, pertechnetate (3%) and colloid (3%) were minor problem. In conclusion, we synthesized seven diamine bisoxime compounds.
Among
them, four EnAO compounds were not labeled by Tc-99m. A BnAO was labeled poorly and two PnAO's were labeled well. These labeling can be explained by tertiary structure of their Tc-99m chelate.
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