Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis

Abstract

Purpose: Many anticancer therapies exert their therapeutic effect by inducing apoptosis in target tumors. We evaluated in a Phase I study the safety and the feasibility of (99m)Tc-Annexin V for imaging chemotherapy-induced apoptosis in human cancers immediately after the first course of chemotherapy.

Experimental design: Fifteen patients presenting with lung cancer (n = 10), lymphoma (n = 3), or breast cancer (n = 2) underwent (99m)Tc-Annexin V scintigraphy before and within 3 days after their first course of chemotherapy. Tumor response was evaluated by computed tomography and (18)F-fluoro-2-deoxy-D-glucose positron emission tomography scans, 3 months in average after completing the treatment. Median follow-up was 117 days.

Results: In all cases, no tracer uptake was observed before treatment. However, 24-48 h after the first course of chemotherapy, 7 patients who showed (99m)Tc-Annexin V uptake at tumor sites, suggesting apoptosis, had a complete (n = 4) or a partial response (n = 3). Conversely, 6 of the 8 patients who showed no significant posttreatment tumor uptake had a progressive disease. Despite the lack of tracer uptake after treatment, the 2 patients with breast cancer had a partial response. Overall survival and progression-free survival were significantly related to tracer uptake in treated lung cancers and lymphomas (P < 0.05). No serious adverse events were observed.

Conclusions: Our preliminary results demonstrated the feasibility and the safety of (99m)Tc-Annexin V for imaging apoptosis in human tumors after the first course of chemotherapy. Initial data suggest that early (99m)Tc-Annexin V tumor uptake may be a predictor of response to treatment in-patients with late stage lung cancer and lymphoma.