Synthesis and preliminary biological evaluation of (3-iodobenzoyl)norbiotinamide and ((5-iodo-3-pyridinyl)carbonyl)norbiotinamide: Two radioiodinated biotin conjugates with improved stability

A new class of radioiodinated biotin conjugates is described in which the amido bond between biotin and the labeled prosthetic group is reversed. One conjugate, (3-[I-125]iodobenzoyl)norbiotinamide (4c, [I-125]IBB) was labeled with (NaI)-I-125 in one step from (3-(tributylstannyl)benzoyl)norbiotinamide (4b, TBB) via a demetalation reaction. However, the analogous reaction with ((5-(tributylstannyl)-3-pyridinyl)carbonyl) norbiotinamide (6b, TPB) failed to yield ((5-[I-131]iodo-3-pyridinyl)carbonyl)norbiotinamide (6c, [I-131]IPB), necessitating a two-step approach for synthesizing [I-131]IPB. The binding of [I-125]IBB and [I-131]IPB to streptavidin in vitro was identical to that of biotinyl-3-[I-125]iodoanilide, a conjugate with an amido bond with normal configuration. Both [I-125]IBB and [I-131]IPB were stable in serum while the first-generation compound was rapidly degraded. The biodistribution patterns of [I-125]IBB and [I-131]IPB in mice are consistent with limited degradation of these conjugates by biotinidase and deiodinases.