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Division of Nuclear Medicine [T. B., R. H., P. R.], Pneumology [P. B.], Oncology [G. J.], and Biostatistics and Epidemiology [L. S.], University Hospital of Liège, 4000 Liège, Belgium, and Theseus Imaging Corporation, Boston, Massachusetts 02111 [N. S., A. G.]
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 99mTc-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 99mTc-Annexin V scintigraphy before and within 3 days after their first course of chemotherapy. Tumor response was evaluated by computed tomography and 18F-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, 2448 h after the first course of chemotherapy, 7 patients who showed 99mTc-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 99mTc-Annexin V for imaging apoptosis in human tumors after the first course of chemotherapy. Initial data suggest that early 99mTc-Annexin V tumor uptake may be a predictor of response to treatment in-patients with late stage lung cancer and lymphoma.
Commentary
Clin. Cancer Res. 2002 8: 2757-2758.
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