UNLABELLED: Gene therapy trials would benefit greatly from the use of noninvasive imaging to determine the location, magnitude, and time course of gene transfer. Somatostatin receptor subtype 2 (SSTR2) has been used as a reporter probe for gamma-camera imaging of gene transfer in animal models. PET has greater sensitivity than gamma-camera imaging and therefore would have an advantage for the imaging of SSTR2 gene transfer. METHODS: An adenovirus (AdHASSTR2) carrying sstr2, which encodes an N-terminal hemagglutinin epitope, was used for evaluating SSTR2 gene transfer. The somatostatin analog Demotate 1 (Tyr(3)-octreotate conjugated to the 1,4,8,11-tetraazaundecane chelator) was used for chelation of the positron emitter (94m)Tc (half-life, 52 min) and targeting to SSTR2. Gene transfer was evaluated in vitro with A-427 non-small cell lung cancer cells after infection with AdHASSTR2 by (94m)Tc-Demotate 1 binding and internalization assays. In vivo biodistribution and microPET studies were conducted with mice bearing A-427 tumor xenografts directly injected with AdHASSTR2 to determine the tumor localization of (94m)Tc-Demotate 1. RESULTS: (94m)Tc-Demotate 1 bound with high affinity and was internalized rapidly into AdHASSTR2-infected A-427 cells. Biodistribution studies showed uptake of (94m)Tc-Demotate 1 in tumors infected with AdHASSTR2 (4.0 percentage injected dose per gram [%ID/g] at 2 h) and background uptake in tumors infected with a control adenovirus (0.8 %ID/g at 2 h). The uptake of (94m)Tc-Demotate 1 in AdHASSTR2-infected tumors was greater than the uptake in all other tissues, except for the kidneys and the SSTR2-positive pancreas. MicroPET imaging showed similar results, with clear uptake of (94m)Tc-Demotate 1 in AdHASSTR2-infected tumors, background uptake in control tumors, and clearance through the kidneys. CONCLUSION: These studies show that the positron-emitting somatostatin analog (94m)Tc-Demotate 1 could be used to determine SSTR2 gene transfer by microPET imaging, a result that will improve the sensitivity of the SSTR2 reporter gene system.
UNLABELLED: Gene therapy trials would benefit greatly from the use of noninvasive imaging to determine the location, magnitude, and time course of gene transfer. Somatostatin receptor subtype 2 (SSTR2) has been used as a reporter probe for gamma-camera imaging of gene transfer in animal models. PET has greater sensitivity than gamma-camera imaging and therefore would have an advantage for the imaging of SSTR2 gene transfer. METHODS: An adenovirus (AdHASSTR2) carrying sstr2, which encodes an N-terminal hemagglutinin epitope, was used for evaluating SSTR2 gene transfer. The somatostatin analog Demotate 1 (Tyr(3)-octreotate conjugated to the 1,4,8,11-tetraazaundecane chelator) was used for chelation of the positron emitter (94m)Tc (half-life, 52 min) and targeting to SSTR2. Gene transfer was evaluated in vitro with A-427 non-small cell lung cancer cells after infection with AdHASSTR2 by (94m)Tc-Demotate 1 binding and internalization assays. In vivo biodistribution and microPET studies were conducted with mice bearing A-427 tumor xenografts directly injected with AdHASSTR2 to determine the tumor localization of (94m)Tc-Demotate 1. RESULTS: (94m)Tc-Demotate 1 bound with high affinity and was internalized rapidly into AdHASSTR2-infected A-427 cells. Biodistribution studies showed uptake of (94m)Tc-Demotate 1 in tumors infected with AdHASSTR2 (4.0 percentage injected dose per gram [%ID/g] at 2 h) and background uptake in tumors infected with a control adenovirus (0.8 %ID/g at 2 h). The uptake of (94m)Tc-Demotate 1 in AdHASSTR2-infected tumors was greater than the uptake in all other tissues, except for the kidneys and the SSTR2-positive pancreas. MicroPET imaging showed similar results, with clear uptake of (94m)Tc-Demotate 1 in AdHASSTR2-infected tumors, background uptake in control tumors, and clearance through the kidneys. CONCLUSION: These studies show that the positron-emitting somatostatin analog (94m)Tc-Demotate 1 could be used to determine SSTR2 gene transfer by microPET imaging, a result that will improve the sensitivity of the SSTR2 reporter gene system.
Authors: Ron Chen; Jesse J Parry; Walter J Akers; Mikhail Y Berezin; Issam M El Naqa; Samuel Achilefu; W Barry Edwards; Buck E Rogers Journal: J Nucl Med Date: 2010-08-18 Impact factor: 10.057
Authors: Mai Johnson; Breanne D W Karanikolas; Saul J Priceman; Russell Powell; Margaret E Black; Hsiao-Ming Wu; Johannes Czernin; Sung-Cheng Huang; Lily Wu Journal: J Nucl Med Date: 2009-04-16 Impact factor: 10.057
Authors: Wael R Abd-Elgaliel; Fabio Gallazzi; Jered C Garrison; Tammy L Rold; Gary L Sieckman; Said Daibes Figueroa; Timothy J Hoffman; Susan Z Lever Journal: Bioconjug Chem Date: 2008-09-23 Impact factor: 4.774