BIODISTRIBUTION OF IN-111-LABELED SCN-BZ-DTPA-BC-2 MAB FOLLOWING LOCO-REGIONAL INJECTION INTO GLIOBLASTOMAS

We analyzed the biodistribution of the In-111-labelled murine anti-ten ascin-C MAb BC-2 after intralesional injection in 15 glioblastoma pati ents. The activated ligand DTPA was conjugated via the isothiocyanato- benzyl group onto BC-2. Conjugates were labelled with In-111, displayi ng immunoreactivity greater than 90% and labelling efficiency of 99 +/ - 1%, in contrast to i,v. injections, excellent tumor uptake was obtai ned by direct intralesional injection of conjugates that showed only s low systemic release, In serum, conjugates were found to be intact; in urine, only low molecular-weight decay products were detected. In 8 p atients, outflow from the site of injection into systemic circulation was low; daily activity in the serum and urine was found to be below 2 % of the total injected radioactivity; most of the injected activity w as retained within the tumor, resulting in effective half-lives of 58 +/- 5 hr, In contrast, higher outflow up to 10% of regionally injected In-111-DTPA-BC-2 MAb into systemic circulation resulted in considerab le shortening of the effective half-lives to 20 to 40 hr in 7 patients . This outflow was found to correlate with tumor size and blood/brain barrier disruption. In one patient, HPLC analysis of tumor cyst fluid 3 and 6 days after intralesional injection revealed conjugates to be i ntact and allowed the estimate of about 70% of the total injected In-1 11-DTPA-BC-2 to be confined to tumor tissue. We conclude that differen t outflow patterns can be observed following locoregional injection of (111)n-DTPA-BC-2, leading to considerable variations in the effective half-lives of isotopes within the tumor, requiring adjustment of the radiation dose in therapeutic trials. (C) 1997 Wiley-Liss, Inc.