Exogenous gene expression in tumors: noninvasive quantification with functional and anatomic imaging in a mouse model.
OBJECTIVE
To assess whether a combination of functional (planar imaging and single photon emission computed tomography [SPECT]) and anatomic (magnetic resonance [MR] imaging) imaging techniques can be used to noninvasively quantify tumor expression of a somatostatin receptor type 2A (SSTR2A) gene chimera in vivo.


METHODS
All animal experiments were approved by the institutional animal care and use committee. Expression of the SSTR2A gene chimera was quantified in vitro, in vivo, and ex vivo. The epitope tag of the fusion protein was detected through an antibody, and the receptor portion was detected by using the Food and Drug Administration-approved radiopharmaceutical indium 111 octreotide. Six mice were injected with cells transfected with vector and with two clonal cell lines that each expressed different amounts of the gene chimera. With a dedicated small-animal gamma camera, planar imaging and SPECT were used for quantification of radiopharmaceutical uptake in vivo; 4.7-T MR imaging was used to derive tumor weight. After imaging, excised tumors were evaluated for uptake and weight. For statistical analysis, linear regression analysis, Wilcoxon rank sum test, and Kruskal-Wallis test were employed.


RESULTS
Different expression levels of the chimeric gene were confirmed in vitro. Radiopharmaceutical uptake assessed in excised tumors and that derived from in vivo planar (r = 0.94, P < .05, n = 18) or SPECT (r = 0.90, P < .05, n = 18) images correlated. Weight of excised tumors and that derived from MR images (r = 0.98, P < .05, n = 18) correlated. MR images also allowed morphologic assessment. The biodistribution parameter of percentage of injected dose per gram of excised tumors correlated with the same measure derived from a combination of planar (r = 0.90, P < .05, n = 18) or SPECT (r = 0.87, P < .05, n = 18) images and MR images.


CONCLUSIONS
A combination of noninvasive functional and anatomic imaging can be used in vivo to quantify gene transfer in tumors.
Yang
Dan
D
Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Han
Lin
L
Kundra
Vikas
V
D000818:Animals; D002678:Chimera; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000032:analysis / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon
D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2