Authors: Jae Hoon Shin JuneKey Chung Joo Hyun Kang Yong Jin Lee Kwang Il Kim Chul Woo Kim Jae Min Jeong Dong Soo Lee Myung Chul Lee
Publish Date: 2003/12/19
Volume: 31, Issue: 3, Pages: 425-432
Abstract
Positron emission tomography PET imaging reporter genes such as HSV1tk and D2 receptor genes make it possible to visualise gene expression noninvasively and repetitively in vivo However these systems require the synthesis of complicated substrates and the availability of expensive PET equipment Expression of the sodium/iodide symporter NIS gene can be easily monitored with radioiodines and technetium99m using a gamma camera To evaluate the possibility of using NIS as an imaging reporter gene we compared its characteristics with those of the conventional HSV1tk gene The CM cell line was made by transfecting the HSV1tk gene into CT26 mouse colon carcinoma cell line The CTN and CMN cell lines were then made by transfecting the NIS gene into CT26 and CM We measured the uptake of iodine125 iodovinyldeoxyuridine 125IIVDU and 125I to evaluate the expression of the HSV1tk and NIS genes respectively Each cell line was injected into four flank sites in Balb/c mice The biodistribution study was performed after intravenously injecting 125IIVDU and 131I and 131I scintigraphy was performed for the evaluation of NIS expression In vitro studies indicated that CTN and CMN had 40 to 79fold and 150 to 256fold higher uptake of 125I than CT26 and CM respectively Furthermore CM and CMN showed 57 to 69fold higher uptake of 125IIVDU than CT26 and CTN NIS gene expression and 125I accumulation were found to be directly correlated R 2=0923 as were HSV1tk gene expression and 125IIVDU accumulation R 2=0956 Calculated signal per unit NIS and HSV1tk mRNA expression was 23240±3755 cpm and 34039±5346 cpm respectively In vivo study indicated that CTN and CMN had 23 and 58fold higher uptake of 131I than CT26 and CM and 18 and 35fold higher uptake of 125IIVDU than CT26 and CTN Scintigraphy using 131I easily visualised CTN and CMN tumours In conclusion the NIS gene may be viewed as an imaging reporter gene with comparable performance to the HSV1tk gene for monitoring target gene expression
Keywords: