MicroPET imaging of gene transfer with a somatostatin receptor-based reporter gene and 94mTc-demotate 1

Buck E. Rogers, Jesse J. Parry, Rebecca Andrews, Paul Cordopatis, Berthold A. Nock, Theodosia Maina

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52 Scopus citations

Abstract

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 γ-camera imaging of gene transfer in animal models. PET has greater sensitivity than γ-camera imaging and therefore would have an advantage for the imaging of SSTR2 gene transfer. Methods: An adenovirus (AdHASSTR2) carrying ssfr2, 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 94mTc (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 94mTc-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 94mTc-Demotate 1. Results: 94mTc-Demotate 1 bound with high affinity and was internalized rapidly into AdHASSTR2-infected A-427 cells. Biodistribution studies showed uptake of 94mTc-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 94mTc-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 94mTc-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 94mTc-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.

Original languageEnglish
Pages (from-to)1889-1897
Number of pages9
JournalJournal of Nuclear Medicine
Volume46
Issue number11
StatePublished - Nov 1 2005

Keywords

  • Adenovirus
  • Gene transfer
  • PET
  • Somatostatin receptor
  • Tc

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    Rogers, B. E., Parry, J. J., Andrews, R., Cordopatis, P., Nock, B. A., & Maina, T. (2005). MicroPET imaging of gene transfer with a somatostatin receptor-based reporter gene and 94mTc-demotate 1. Journal of Nuclear Medicine, 46(11), 1889-1897.