Direct comparison of radiolabeled probes FMAU, FHBG, and FHPG as PET imaging agents for HSV1-tk expression in a human breast cancer model.
2'-Deoxy-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU), 9-(4-fluoro-3-hydroxy-methyl-butyl)guanine (FHBG) and 9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]-guanine (FHPG) have been evaluated in a human breast cancer model as potential radiotracers for PET imaging of HSV1-tk gene expression. In vitro accumulation of [14C]FMAU, [18F]FHBG, and [18F]FHPG in HSV1-tk-expressing cells was 14- to 16-fold (p <.001), 9- to 13-fold (p <.001), and 2- to 3-fold (p <.05) higher than tk-negative control cells, respectively, between 30 and 240 min. Accumulation of FMAU and FHBG in vector-transduced cells was 10- to 14-fold and 6- to 10-fold higher than wild-type cells, respectively. At 2 hr, uptake of [(14)C]FMAU in tkpositive cells was 6.3-fold and 60-fold higher than [18F]FHBG and [18F]FHPG, respectively. In vivo, tumor uptake of [14C]FMAU in HSV1-tk-expressing cells was 3.7-fold and 5.5-fold (p <.001) higher than tk-negative control cells at 1 and 2 hr, respectively. Tumor uptake of [18F]FHBG was 4.2-fold and 12.6-fold higher (p <.001) than tk-negative cells at the same time points. Incorporation of [14C]FMAU in tk-positive tumor was 18-fold and 24-fold higher (p <.001) than [18F]FHBG at 1 and 2 hr, respectively. Micro-PET images support the biodistribution results and indicate that both [18F]FMAU and [18F]FHBG are useful for imaging HSV1-tk expression in breast cancer. Although FMAU demonstrates higher total incorporation (%dose/g) in tumor tissue compared with the other tracers, FHBG is superior in terms of specific accumulation in transfected cells at later time points.
University of Southern California, USA.
Mian M
MM
Alauddin
Atranik
A
Shahinian
Erlinda M
EM
Gordon
Peter S
PS
Conti
D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D003952:Diagnostic Imaging; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006147:Guanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013937:Thymidine Kinase / Q000235:genetics; D013997:Time Factors; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
C471398:9-(3-fluoro-1-hydroxy-2-propoxy)methylguanine; C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; D006147:Guanine; D013937:Thymidine Kinase; C034935:clevudine; D015774:Ganciclovir