A RADIOIODINATED BIOCYTIN DERIVATIVE FOR IN-VIVO APPLICATIONS

Radioiodinated biocytin derivatives are potentially useful for multi-s tep tumour targeting using the avidin-biotin system. We synthesized a radioiodinated biocytin derivative and evaluated its properties in viv o. We labelled biocytin with I-125 by coupling biocytin to radioiodina ted N-succinimidyl 3-(tri-n-butyl-stannyl) benzoate, and assessed its binding to avidin and its biodistribution in normal and tumour-bearing mite. When the synthesized biocytin was incubated with immobilized av idin, more than 94% of the radioactivity was bound. However, after 2 h incubation in serum, only 40% of the radioactivity was bound to the a vidin. The iodinated biocytin derivative was characteristically taken up by the liver and the kidneys when injected intravenously into mice. In mice bearing an intraperitoneal tumour xenograft,I-125-biocytin an d In-111-biotin were co-injected intraperitoneally 4 h after the intra peritoneal administration of avidin, which accumulated in the intraper itoneal tumours. At 2 and 24 h, the tumour uptake of I-125-biocytin wa s 8.2 and 3.8% ID/g respectively, whereas that of In-111-biotin was 20 .0 and 18.7% ID/g respectively. When radioiodinated, biocytin retains its binding capacity to avidin, and it localizes well with high tumour -to-normal tissue ratios early post-injection using the two-step metho d, but compared to In-111-biotin it is unstable. We conclude that the stability of the product in serum needs to be improved prior to in-viv o applications. ((C) 1998 Lippincott Williams & Wilkins).