A Phase I safety and imaging study using radiofrequency ablation (RFA) followed by 131 I

Summary Biologic therapy of solid tumors with monoclonal antibodies has been difficult due to poor antibody localization and heterogeneous expression of target antigens. TNT-1/B is a murine-human monoclonal antibody that recognizes a DNA/histone 1 epitope and concentrates in necrotic tissue and is now available as genetically engineered murinehuman chimeric (ch) construct. Thus, the binding of chTNT-1/B to areas of necrosis in tumors has potential to treat a very wide variety of cancers. Since radiofrequency ablation (RFA) of tumor nodules reliably produces 1-5 cm zones of >99% necrotic tissue, RFA may create abundant binding sites for chTNT-1/B, regardless of initial tumor histology. Study design and results: Hepatic distribution and safety of iv 131 I-chTNT-1/B (Peregrine Pharmaceuticals, Tustin CA) given after RFA of hepatic metastases was evaluated in six patients. Five of 6 had metastatic disease confined to the liver. Diagnoses included carcinoid, leiomyosarcoma, colon adenocarcinoma and islet cell carcinoma. RFA of metastases was done in a standard manner under ultrasound guidance using the RITA device. Liver function tests were monitored sequentially after RFA Patients were eligible to receive the 131 I radiolabeled antibody when AST and ALT were ≤ CTC grade 3 and also decreased on 2 successive days and performance was acceptable for the procedure. Patients that had the RFA procedure done percutaneously received the 131 I -chTNT-1/B at 3, 3, 4, and 6 days after the procedure. The two patients having RFA intraoperatively received the 131 I-chTNT-1/B somewhat later (6 and 10 days). Patients received 0.35 mCi/Kg or 0.71 mCi/Kg 131 IchTNT-1/B; total doses ranged between 22 and 55 mCi. Infusions were given over 30 minutes; no infusion toxicity was seen. Between 12 to 29% (Mean 28.1 +/- 4.0%) of an injected dose concentrated in the liver. Gamma camera imaging confirmed selective and avid targeting of radioisotope to areas of RFA within the liver. No significant adverse events were observed. Conclusion: The chTNT-1/B construct has excellent potential to become useful after RFA. Zones of necrosis that facilitate 131 I-chTNT-1/B antibody binding were probably created after RFA. A further improvement in patient convenience and specific targeting with this promising immunoconjugate may also be possible using direct antibody injection at the end of the RFA procedure into the zone of necrosis using temperature monitoring.