In vivo imaging of HIV protease activity in amplicon vector-transduced gliomas.
In vivo imaging of endogenously expressed mammalian proteases has been useful for the detection of cancer and preneoplastic lesions, for staging of inflammatory and autoimmune diseases, and for testing the efficacy of novel protease inhibitors. Here we report on the synthesis of a novel imaging probe that is specific for HIV-1 protease (PR). The probe was designed to be biocompatible, i.v. injectable, and detectable by fluorescence imaging. Human Gli36 glioblastoma cells infected with an human simplex virus amplicon vector expressing HIV-1PR showed specific fluorescence activation, an effect that could be inhibited by the HIV-1PR inhibitor, indinavir. The transfer of the HIV-1PR marker gene could be detected in vivo after intratumoral delivery of the human simplex virus-amplicon vector. These results are the first proof of principle that viral proteases can directly be imaged in vivo. These findings may be directly applicable in using viral protease expression as a transgene marker in tumor therapy and may have implications in testing the efficacy of HIV-1PR inhibitors in vivo.
Shah
Khalid
K
Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA. Weissleder@helix.mgh.harvard.edu
Tung
Ching-Hsuan
CH
Chang
Chung-Hsun
CH
Slootweg
Eric
E
O'Loughlin
Terence
T
Breakefield
Xandra O
XO
Weissleder
Ralph
R
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms; D002522:Chlorocebus aethiops; D005819:Genetic Markers; D005822:Genetic Vectors; D005909:Glioblastoma; D005910:Glioma / Q000201:enzymology* / Q000821:virology; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D000970:Antineoplastic Agents; D005819:Genetic Markers; D017320:HIV Protease Inhibitors; D016333:HIV Protease