In vivo fate of folate-BSA in non-tumor- and tumor-bearing mice

KB tumor cells exhibit an increased number of folate receptors on their mem brane. This receptor has been proposed as a promising target for tumor drug targeting. Therefore, the disposition of folate-conjugated bovine serum al bumin (folate-BSA) was examined as a model system for drug targeting. Nude mice which had received KB tumor cell transplants were given bolus intraven ous administration of either In-111-labeled folate-BSA (In-111-folate-BSA; 1 mg/kg) or unmodified In-111-BSA (In-111-BSA; 1 mg/kg). The disposition ch aracteristics and pharmacokinetics of In-111-folate-BSA were compared with those of the In-111-BSA as a control. The half-life of the beta-phase of In -111-folate-BSA in plasma was 140 min. The tumor uptake rate index for In-1 11-folate-BSA was 0.46 mu L/min/g, and that for In-111-BSA was 0.32 mu L/mi n/g. This index of In-111-folate-BSA was slightly higher than that of In-11 1-BSA in vivo, by a factor of 1.4. In vivo experiments showed folate-BSA ha s a relatively long plasma duration. In-111-folate-BSA also showed selectiv e distribution to tumors, but not as great as recent results from in vitro experiments. Therefore, the low vascular permeability of BSA into solid tum or tissue and inhibition of folate-mediated In-111-folate-BSA uptake by tum or cells from the blood may be the rate-limiting factor of distribution.