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Feasibility of ^99mTc-Annexin V for Repetitive Detection of Apoptotic Tumor Response to Chemotherapy: An Experimental Study Using a Rat Tumor Model

¹ Department of Tracer Kinetics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
² Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
³ Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan
⁴ Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
⁵ Pediatric Radiology, Stanford University School of Medicine, Palo Alto, California
⁶ Department of Laboratory Medicine, University of Washington, Seattle, Washington

Annexin V (annexin A5), a human protein with a high affinity for phosphatidylserine, labeled with ^99mTc can detect apoptosis in vivo. In the repetitive detection of apoptosis with ^99mTc-annexin V, however, the specific binding of annexin V to phosphatidylserine might affect the subsequent detection of apoptosis with this compound. To determine whether there is interference with repetitive doses of annexin V, we evaluated the effects of previous administration of cold annexin V on accumulation of ^99mTc-annexin V in tumors in an experimental tumor model. Methods: Rats bearing hepatoma received cyclophosphamide (150 mg/kg, intraperitoneally) 11 d after the tumor inoculation. Cold annexin V (20 µg/kg, intravenously) was administered 24 h before or after the cyclophosphamide treatment (n = 7/group). ^99mTc-Annexin V was injected intravenously (radioactive dose, 5–23 MBq/kg; mass dose, 20 µg/kg), and radioactivity in tissues was determined 6 h later. Results: Accumulation of ^99mTc-annexin V in tumors was not significantly affected by previous treatment with cold annexin V before or after chemotherapy. Conclusion: These results demonstrate the feasibility of ^99mTc-annexin V imaging for repetitive detection of apoptosis, which is highly required in the clinical setting.

Key Words: ^99mTc-annexin V • apoptosis • tumor • chemotherapy • rat

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