Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene

PURPOSE: Previous work showed quantitative imaging of T-cell migration into a tumor site by positron emission tomography (PET), using retroviral transduction of mutated thymidine kinase (sr39TK) reporter genes into immunized T-lymphocytes. PROCEDURES AND RESULTS: In order to improve the sensitivity and flexibility of the imaging analysis, lentivirus, that expressed sr39TK, was used to transduce the lymphocytes that migrated to an immunogenic sarcoma site. In comparison to retrovirally transduced lymphocytes, the lentivirally transduced lymphocytes showed enhanced PET signal when equal numbers of transduced lymphocytes were transferred. Furthermore, in order to utilize multimodality in vivo imaging capability, a tri-fusion reporter gene containing sr39TK, synthetic Renilla luciferase (hRluc), and enhanced green florescent protein (eGFP) was inserted into a lentiviral transfer vector. Using the adoptive transfer model, tumor-specific lymphocytic migration was detected by both microPET scan and bioluminescence imaging. CONCLUSION: The multimodal imaging strategy coupled with lentiviral reporter construct delivery demonstrated here can facilitate future molecular imaging studies. (C) 2004 Elsevier Inc. All rights reserved.