Positron Emission Tomography Imaging of Adenoviral-Mediated Transgene Expression in Liver Cancer Patients

Background & Aims: In gene-therapy protocols, imaging of gene expression is needed to evaluate the transduction efficiency of the vector, its tissue distribution, and the duration of transgene expression and to assess the feasibility of repeated vector administration. Methods: We have used positron emission tomography with a fluorine-18-labeled penciclovir analogue to monitor thymidine kinase gene expression after intratumoral injection of a first-generation recombinant adenovirus in patients with hepatocellular carcinoma. Patients were enrolled in a pilot clinical trial and treated with escalating doses of the vector. Two days after adenovirus inoculation, transgene expression was evaluated during the first hours after administration of the radiotracer both on the treated lesion and on a whole-body basis. Results: Transgene expression in the tumor was dependent on the injected dose of the adenovirus and was detectable in all patients who received ≥10¹² viral particles. However, when the study was repeated 9 days after vector injection, no expression could be observed. It is interesting to note that no specific expression of the transgene could be detected in distant organs or in the surrounding cirrhotic tissue in any of the cases studied. Conclusions: Our findings show the real possibility of imaging transgene expression in humans by using viral vectors. We show that hepatocarcinoma is a permissive tumor for adenoviral infection and that the nontumoral cirrhotic liver is spared from transduction when the vector is administered by intratumoral injection. These results show that positron emission tomography imaging may help in the design of gene-therapy strategies and in the clinical assessment of new-generation vectors.

Abbreviations used in this paper:  CT, computerized tomography , [¹⁸F]FHBG, [¹⁸F]9-(4-[¹⁸F]-fluoro-3-hydroxymethylbutyl)-guanine , [¹²⁴I]FIAU, 5-[¹²⁴I]iodo-2′-fluoro-2′-deoxy-1-β-d-arabinofuranosyl-5-iodouracil , HCC, hepatocellular carcinoma , HSV1-tk, herpes simplex virus thymidine kinase , PET, positron emission tomography , SUV, standard uptake value , vp, viral particle