SYNTHESIS AND PRELIMINARY BIOLOGICAL EVALUATION OF (3-IODOBENZOYL)NORBIOTINAMIDE AND ((5-IODO-3-PYRIDINYL)CARBONYL)NORBIOTINAMIDE - 2 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 reve rsed. 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)carbon yl) norbiotinamide (6b, TPB) failed to yield (5-[I-131]iodo-3-pyridiny l)carbonyl)norbiotinamide (6c, [I-131]IPB), necessitating a two-step a pproach 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 configur ation. Both [I-125]IBB and [I-131]IPB were stable in serum while the f irst-generation compound was rapidly degraded. The biodistribution pat terns of [I-125]IBB and [I-131]IPB in mice are consistent with limited degradation of these conjugates by biotinidase and deiodinases.