In vivo evaluation of 2'-deoxy-2'-[(18)F]fluoro-5-iodo-1-beta-D-arabinofuranosyluracil ([18F]FIAU) and 2'-deoxy-2'-[18F]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil ([18F]FEAU) as markers for suicide gene expression.
OBJECTIVE
FIAU and FEAU were evaluated in vitro and in vivo as markers for HSV1-tk gene expression.


METHODS
In vitro and biodistribution studies were performed in wild type and transduced HT-29 cells using [14C]FIAU and [3H]FEAU. PET imaging was performed using [18F]FIAU and [18F]FEAU.


RESULTS
In vitro uptake of [14C]FIAU in tk-positive cells was 39-fold, 49-fold, and 43-fold higher (p<0.001) than in wild type cells at 30, 60, and 120 min, respectively. Uptake of [3H]FEAU in transduced cells was 46-fold, 62-fold, and 121-fold higher (p<0.001) than in wild type cells at the same time points. In vivo uptake of [14C]FIAU at 2 h in HSV1-tk positive tumors was 15.48+/-3.94, 6.7-fold higher (p<0.001) than in wild type tumors. Uptake of [3H]FEAU in transduced tumors was 9.98+/-1.99, 5.0-fold higher (p<0.001) than in wild type tumors. Micro-PET images using [18F]FIAU and [18F]FEAU also showed very high uptake in HSV-tk tumors.


CONCLUSIONS
[18F]FIAU and [18F]FEAU appear to be potential PET imaging agents for gene expression.
Alauddin
Mian M
MM
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. T8.3895, P.O. Box 059, Houston, TX 77030, USA. alauddin@di.mdacc.tmc.edu
Shahinian
Antranic
A
Park
Ryan
R
Tohme
Michel
M
Fissekis
John D
JD
Conti
Peter S
PS
D000818:Animals; D001086:Arabinofuranosyluracil / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D004247:DNA / Q000378:metabolism; D005462:Fluorine Radioisotopes; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005821:Genetic Techniques; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000295:instrumentation / Q000379:methods; D019275:Radiopharmaceuticals / Q000494:pharmacology; D013937:Thymidine Kinase / Q000378:metabolism
D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; D004247:DNA; D013937:Thymidine Kinase