PURPOSE: This study aims to use a simple, quantitative method to compare the HSV1sr39TK/(18) F-FHBG PET reporter gene/PET reporter probe (PRG/PRP) system with PRGs derived from human nucleoside kinases. PROCEDURES: The same adenovirus vector is used to express alternative PRGs. Equal numbers of vectors are injected intravenously into mice. After PRP imaging, quantitative hepatic PET signals are normalized for transduction by measuring hepatic viral genomes. RESULTS: The same adenovirus vector was used to express equivalent amounts of HSV1sr39TK, mutant human thymidine kinase 2 (TK2-DM), and mutant human deoxycytidine kinase (dCK-A100VTM) in mouse liver. HSV1sr39TK expression was measured with (18) F-FHBG, TK2-DM and dCK-A100VTM with (18) F-L-FMAU. TK2-DM/(18) F-L-FMAU and HSV1sr39TK/(18) F-FHBG had equivalent sensitivities; dCK-A100VTM/(18) F-L-FMAU was twice as sensitive as HSV1sr39TK/(18) F-FHBG. CONCLUSIONS: The human PRG/PRP sensitivities are comparable and/or better than HSV1sr39TK/(18) F-FHBG. However, for clinical use, identification of the best PRP substrate for each enzyme, characterization of probe distribution, and consequences of overexpressing nucleoside kinases must be evaluated.
PURPOSE: This study aims to use a simple, quantitative method to compare the HSV1sr39TK/(18) F-FHBG PET reporter gene/PET reporter probe (PRG/PRP) system with PRGs derived from humannucleoside kinases. PROCEDURES: The same adenovirus vector is used to express alternative PRGs. Equal numbers of vectors are injected intravenously into mice. After PRP imaging, quantitative hepatic PET signals are normalized for transduction by measuring hepatic viral genomes. RESULTS: The same adenovirus vector was used to express equivalent amounts of HSV1sr39TK, mutant humanthymidine kinase 2 (TK2-DM), and mutant humandeoxycytidine kinase (dCK-A100VTM) in mouse liver. HSV1sr39TK expression was measured with (18) F-FHBG, TK2-DM and dCK-A100VTM with (18) F-L-FMAU. TK2-DM/(18) F-L-FMAU and HSV1sr39TK/(18) F-FHBG had equivalent sensitivities; dCK-A100VTM/(18) F-L-FMAU was twice as sensitive as HSV1sr39TK/(18) F-FHBG. CONCLUSIONS: The humanPRG/PRP sensitivities are comparable and/or better than HSV1sr39TK/(18) F-FHBG. However, for clinical use, identification of the best PRP substrate for each enzyme, characterization of probe distribution, and consequences of overexpressing nucleoside kinases must be evaluated.
Authors: Dean O Campbell; Shahriar S Yaghoubi; Ying Su; Jason T Lee; Martin S Auerbach; Harvey Herschman; Nagichettiar Satyamurthy; Johannes Czernin; Arnon Lavie; Caius G Radu Journal: J Biol Chem Date: 2011-11-09 Impact factor: 5.157
Authors: S Yaghoubi; J R Barrio; M Dahlbom; M Iyer; M Namavari; N Satyamurthy; R Goldman; H R Herschman; M E Phelps; S S Gambhir Journal: J Nucl Med Date: 2001-08 Impact factor: 10.057
Authors: S S Gambhir; E Bauer; M E Black; Q Liang; M S Kokoris; J R Barrio; M Iyer; M Namavari; M E Phelps; H R Herschman Journal: Proc Natl Acad Sci U S A Date: 2000-03-14 Impact factor: 11.205
Authors: Johannes Schwarzenberg; Caius G Radu; Matthias Benz; Barbara Fueger; Andrew Q Tran; Michael E Phelps; Owen N Witte; Nagichettiar Satyamurthy; Johannes Czernin; Christiaan Schiepers Journal: Eur J Nucl Med Mol Imaging Date: 2010-12-03 Impact factor: 9.236
Authors: Jason T Lee; Hanwen Zhang; Maxim A Moroz; Yury Likar; Larissa Shenker; Nikita Sumzin; Jose Lobo; Juan Zurita; Jeffrey Collins; R Michael van Dam; Vladimir Ponomarev Journal: Mol Imaging Biol Date: 2017-02 Impact factor: 3.488