BIOTINYLATED IODO-POLYLYSINE FOR PRETARGETED RADIATION DELIVERY

Effects to achieve rapid specific targeting of radioisotopes to diseas e processes using antibodies conjugated with avidin or streptavidin fo r pretargeting and radiobiotin derivatives for isotope delivery are at tracting substantial interest. At present, these approaches appear to be limited by low delivery of radiotracer to the target. As an alterna te radiobiotin tracer, biotinylated/iodinated polylysine (BIP) was pre pared by conjugating poly-L-lysine (MW almost-equal-to 10,200) with bi otin succinimide esters and the Bolton-Hunter reagent. This reagent wa s then radioiodinated with I-125 via the Iodogen method. BIP was chara cterized by radio-HPLC and its in vitro binding to streptavidin. The i n vivo localization of BIP was evaluated in a rat model in which strep tavidin agarose beads were physically localized to precapillary arteri oles in the lungs. Biodistribution and blocking studies performed at 4 and 24 hr after BIP injection indicated specific binding and localiza tion of the radiolabeled peptide to the lungs (lung-to-blood ratio alm ost-equal-to 8 at 4 hr postinjection). Comparative studies of BIP and In-111 chelated to biotin showed BIP to have two-fold higher lung targ eting and lower splenic and hepatic uptake than the In-111 biotin deri vative. Our study demonstrates: (1) the feasibility of using a small p eptide as a biotin carrier for pretargeting (and for solubilizing orga nic tracers which may otherwise be difficult to administer in vivo) an d (2) that BIP and BIP-like compounds may be suitable and simple alter natives to radiometal-labeled biotin for pretargeting and may offer im proved targeting to prelocalized streptavidin.