Synthesis of dendrimer-based biotin radiopharmaceuticals to enhance whole-body clearance

To synthesize a biotin radiopharmaceutical that clears rapidly, dendrimer was used as a carrier and conjugated with succinimidyl 3-[(125)I]iodobenzoate and tetrafluorophenyl norbiotinamidosuccinate. Then, succinic anhydride was used to reduce its pI. In mice, the non-succinylated product showed high liver (67% ID/g) and kidney (44% ID/g) uptakes and whole-body retention (94% ID) at 20 min that persisted for 12 hr. The corresponding organ uptakes (22% and 11% ID/g) and the whole-body retention (47% ID) were drastically reduced by succinylation (p<0.0001). Lysine co-injection further lowered renal uptake.