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A Simplified Method for Preparation of ^99mTc-Annexin V and its Biologic Evaluation for In Vivo Imaging of Apoptosis After Photodynamic Therapy

¹ Department of Dermatology, University of Wisconsin, Madison, Wisconsin
² Department of Radiation Oncology, The Cleveland Clinic Foundation, Cleveland, Ohio
³ Department of Dermatology, Case Western Reserve University, Cleveland, Ohio
⁴ Department of Pathology, Case Western Reserve University, Cleveland, Ohio

Apoptosis is the likely mechanism behind the effects of chemotherapeutic and radiation treatments, rejection of organ transplants, and cell death due to hypoxic-ischemic injury. A simplified method capable of imaging apoptosis in living animals could have many applications leading to understanding of the involvement of apoptosis in biologic and therapeutic processes. To accomplish this goal we developed a method for the preparation of ^99mTc-annexin V and evaluated its usefulness to detect apoptosis that occurs during tumor shrinkage after photodynamic therapy (PDT). PDT is a cancer treatment modality that leads to rapid induction of apoptosis both in vitro and in in vivo animal models. Methods: A novel synthesis of ^99mTc-annexin V was performed in a simple 1-pot procedure. Radiation-induced fibrosarcoma (RIF-1) tumors grown in C₃H mice were treated with PDT, followed by injection of ^99mTc-annexin V and measurement of its tumor uptake at 2, 4, and 7 h after PDT by autoradiography. Results: The radiochemical purity of ^99mTc-annexin V was >95%. At all time points, ^99mTc-annexin V was clearly imaged in the PDT-treated tumors, whereas the untreated tumors showed no uptake of the radiolabeled compound. Histopathology and immunohistochemistry of PDT-treated tumors confirmed the evidence of apoptosis compared with untreated tumors. Conclusion: These data demonstrate the detection of apoptosis using ^99mTc-annexin V in tumor tissue in living animals after PDT treatment. This novel technique could be used as a noninvasive means to detect and serially image tissues undergoing apoptosis after cancer treatment protocols in humans. Other potential applications of this technique could be the diagnosis of several human disorders, such as myocardial ischemia or infarct, rejection of organ transplantation, and neonatal cerebral ischemia.

Key Words: apoptosis • annexin V • diagnostic imaging • photodynamic therapy • mouse model

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