Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas.

Abstract

We analyzed the biodistribution of the 111In-labelled murine anti-tenascin-C MAb BC-2 after intralesional injection in 15 glioblastoma patients. The activated ligand DTPA was conjugated via the isothiocyanato-benzyl group onto BC-2. Conjugates were labelled with 111In, displaying immunoreactivity greater than 90% and labelling efficiency of 99 +/- 1%. In contrast to i.v. injections, excellent tumor uptake was obtained by direct intralesional injection of conjugates that showed only slow systemic release. In serum, conjugates were found to be intact; in urine, only low-molecular-weight decay products were detected. In 8 patients, 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 was retained within the tumor, resulting in effective half-lives of 58 +/- 5 hr. In contrast, higher outflow up to 10% of regionally injected 111In-DTPA-BC-2 MAb into systemic circulation resulted in considerable 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 intact and allowed the estimate of about 70% of the total injected 111In-DTPA-BC-2 to be confined to tumor tissue. We conclude that different outflow patterns can be observed following locoregional injection of 111In-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.

• Authors: A Merlo, E Jermann, O Hausmann, R Chiquet-Ehrismann, A Probst, H Landolt, H R Maecke, J Mueller-Brand, O Gratzl
• Journal: International journal of cancer (Int J Cancer) Vol. 71 Issue 5 Pg. 810-6 (May 29 1997) ISSN: 0020-7136 [Print] United States
• PMID: 9180150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Indium Radioisotopes
• Tenascin

Topics

• Aged
• Animals
• Antibodies, Monoclonal (administration & dosage, pharmacokinetics)
• Brain Neoplasms (metabolism)
• Female
• Glioblastoma (metabolism)
• Humans
• Indium Radioisotopes
• Kinetics
• Male
• Mice
• Mice, Inbred BALB C
• Middle Aged
• Tenascin (immunology)
• Tissue Distribution