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MicroPET Imaging of Gene Transfer with a Somatostatin Receptor–Based Reporter Gene and ^94mTc-Demotate 1

¹ Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
² Department of Chemistry, University of Patras, Patras, Greece
³ Institute of Radioisotopes–Radiodiagnostic Products, National Center for Scientific Research Demokritos, Athens, Greece

Gene therapy trials would benefit greatly from the use of noninvasive imaging to determine the location, magnitude, and time course of gene transfer. Somatostatin receptor subtype 2 (SSTR2) has been used as a reporter probe for -camera imaging of gene transfer in animal models. PET has greater sensitivity than -camera imaging and therefore would have an advantage for the imaging of SSTR2 gene transfer. Methods: An adenovirus (AdHASSTR2) carrying sstr2, which encodes an N-terminal hemagglutinin epitope, was used for evaluating SSTR2 gene transfer. The somatostatin analog Demotate 1 (Tyr³-octreotate conjugated to the 1,4,8,11-tetraazaundecane chelator) was used for chelation of the positron emitter ^94mTc (half-life, 52 min) and targeting to SSTR2. Gene transfer was evaluated in vitro with A-427 non–small cell lung cancer cells after infection with AdHASSTR2 by ^94mTc-Demotate 1 binding and internalization assays. In vivo biodistribution and microPET studies were conducted with mice bearing A-427 tumor xenografts directly injected with AdHASSTR2 to determine the tumor localization of ^94mTc-Demotate 1. Results: ^94mTc-Demotate 1 bound with high affinity and was internalized rapidly into AdHASSTR2-infected A-427 cells. Biodistribution studies showed uptake of ^94mTc-Demotate 1 in tumors infected with AdHASSTR2 (4.0 percentage injected dose per gram [%ID/g] at 2 h) and background uptake in tumors infected with a control adenovirus (0.8 %ID/g at 2 h). The uptake of ^94mTc-Demotate 1 in AdHASSTR2-infected tumors was greater than the uptake in all other tissues, except for the kidneys and the SSTR2-positive pancreas. MicroPET imaging showed similar results, with clear uptake of ^94mTc-Demotate 1 in AdHASSTR2-infected tumors, background uptake in control tumors, and clearance through the kidneys. Conclusion: These studies show that the positron-emitting somatostatin analog ^94mTc-Demotate 1 could be used to determine SSTR2 gene transfer by microPET imaging, a result that will improve the sensitivity of the SSTR2 reporter gene system.

Key Words: somatostatin receptor • gene transfer • PET • ^94mTc • adenovirus

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JNM 2005 46: 7a-8a. [Full Text]