In vivo functional and anatomic imaging for assessment of in vivo gene transfer.

Abstract

PURPOSE:

To assess whether a combination of in vivo anatomic and functional imaging can help quantify expression of somatostatin receptor type 2 (SSTR2)-based reporters after in vivo gene transfer.

MATERIALS AND METHODS:

All animal experiments were approved by an institutional animal care and use committee. Six nude mice bearing two subcutaneous L3.6pl (human pancreatic cancer) tumors were injected intratumorally with an adenovirus containing a human somatostatin receptor type 2 gene chimera (Ad-HA-SSTR2) or a control adenovirus containing green fluorescent protein (Ad-GFP). Two days later, magnetic resonance (MR) imaging was performed to derive tumor weight and analyze morphology. Intravenous injection of Food and Drug Administration-approved indium 111 octreotide was followed by gamma camera imaging (planar imaging and single photon emission computed tomography [SPECT]) the next day. Region-of-interest analysis followed. The procedure was also performed in six nude mice with slow-growing MDA-MB-435 (human breast carcinoma) tumors, which allowed serial imaging 3 days and 2 weeks after adenovirus injection. After imaging, excised tumor weight and biodistribution were assessed. Statistical analyses included a Student t test and linear regression.

RESULTS:

With both tumor types, ex vivo and image-based in vivo biodistribution demonstrated greater uptake (percentage of injected dose per gram) in tumors infected with Ad-HA-SSTR2 than in those infected with Ad-GFP (P < .05). Furthermore, in vivo and ex vivo biodistribution analysis correlated (ex vivo vs planar and MR imaging: r = 0.87, P < .05, n = 24; ex vivo vs SPECT and MR imaging: r = 0.84, P < .05, n = 24). Moreover, in vivo biodistribution distinguished greater expression at the earlier time point in MDA-MB-435 tumors infected with Ad-HA-SSTR2 from waning expression at the later time point (P < .05).

CONCLUSION:

A combination of in vivo functional and anatomic imaging methods can help quantify gene expression after in vivo gene transfer.

• Authors: Sheela P Singh, Dan Yang, Murali Ravoori, Lin Han, Vikas Kundra
• Journal: Radiology (Radiology) Vol. 252 Issue 3 Pg. 763-71 (Sep 2009) ISSN: 1527-1315 [Electronic] United States
• PMID: 19587310 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Receptors, Somatostatin
• indium-111-octreotide
• Green Fluorescent Proteins
• somatostatin receptor 2
• Octreotide

Topics

• Adenoviridae
• Animals
• Breast Neoplasms (diagnostic imaging)
• Chimera
• Gamma Cameras
• Gene Expression Regulation, Neoplastic
• Gene Transfer Techniques
• Green Fluorescent Proteins
• Linear Models
• Magnetic Resonance Imaging
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neoplasms, Experimental (chemistry, diagnosis, genetics)
• Octreotide (analogs & derivatives)
• Pancreatic Neoplasms (diagnostic imaging, pathology)
• Radiography
• Receptors, Somatostatin (analysis, genetics)
• Tomography, Emission-Computed, Single-Photon