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Published in: Molecular Imaging and Biology 1/2006

01-01-2006 | Original Article

Combined I-124 Positron Emission Tomography/Computed Tomography Imaging of NIS Gene Expression in Animal Models of Stably Transfected and Intravenously Transfected Tumor

Authors: David Dingli, Brad J. Kemp, Michael K. O’Connor, John C. Morris, Stephen J. Russell, Val J. Lowe, MD

Published in: Molecular Imaging and Biology | Issue 1/2006

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Abstract

Purpose

With the advent of replication competent viruses for cancer gene therapy, it has become imperative to monitor the biodistribution, expression and replication of these vectors in living organisms. We evaluated the potential of I-124 positron emission tomography (PET)/computed tomography (CT) imaging in gene therapy animal models utilizing the sodium iodide symporter (NIS) and compared the findings to I-123 gamma camera imaging.

Procedures

CB17 SCID mice were implanted with myeloma cell lines expressing NIS or infected by MV-NIS given systemically. Mice were imaged by both gamma camera (I-123) and PET/CT (I-124 ) and image quality assessed.

Results

NIS expressing tumors concentrated 7.1% of the injected activity while tumors infected with the control virus had only 0.3% of the activity injected.

Conclusions

I-124 PET/CT in combination with NIS allows the tracking of stably transfected tumors or intravenously transfected tumors. Combined modality imaging using PET/CT allows accurate and non-invasive imaging of the distribution and gene expression of a replicating viral vector in living systems.
Literature
1.
go back to reference Kirn D (2001) Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): Results of phase I and II trials. Expert Opin Biol Ther 1:525–538CrossRefPubMed Kirn D (2001) Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): Results of phase I and II trials. Expert Opin Biol Ther 1:525–538CrossRefPubMed
2.
go back to reference Pecora AL, Rizvi N, Cohen GI, et al. (2002) Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol 20:2251–2266CrossRefPubMed Pecora AL, Rizvi N, Cohen GI, et al. (2002) Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol 20:2251–2266CrossRefPubMed
4.
go back to reference Tjuvajev JG, Stockhammer G, Desai R, et al. (1995) Imaging the expression of transfected genes in vivo. Cancer Res 55:6126–6132PubMed Tjuvajev JG, Stockhammer G, Desai R, et al. (1995) Imaging the expression of transfected genes in vivo. Cancer Res 55:6126–6132PubMed
5.
go back to reference Gambhir SS, Herschman HR, Cherry SR, et al. (2000) Imaging transgene expression with radionuclide imaging technologies. Neoplasia 2:118–138PubMedCrossRef Gambhir SS, Herschman HR, Cherry SR, et al. (2000) Imaging transgene expression with radionuclide imaging technologies. Neoplasia 2:118–138PubMedCrossRef
6.
go back to reference Herschman HR, MacLaren DC, Iyer M, et al. (2000) Seeing is believing: Non-invasive, quantitative and repetitive imaging of reporter gene expression in living animals, using positron emission tomography. J Neurosci Res 59:699–705CrossRefPubMed Herschman HR, MacLaren DC, Iyer M, et al. (2000) Seeing is believing: Non-invasive, quantitative and repetitive imaging of reporter gene expression in living animals, using positron emission tomography. J Neurosci Res 59:699–705CrossRefPubMed
7.
go back to reference Dingli D, Russell SJ, Morris JC (2003) In vivo imaging and tumor therapy with the sodium iodide symporter. J Cell Biochem 90:1079–1086CrossRefPubMed Dingli D, Russell SJ, Morris JC (2003) In vivo imaging and tumor therapy with the sodium iodide symporter. J Cell Biochem 90:1079–1086CrossRefPubMed
8.
go back to reference Spitzweg C, Morris JC (2001) Approaches to gene therapy with sodium/iodide symporter. Exp Clin Endocrinol Diabetes 109:56–59CrossRefPubMed Spitzweg C, Morris JC (2001) Approaches to gene therapy with sodium/iodide symporter. Exp Clin Endocrinol Diabetes 109:56–59CrossRefPubMed
9.
go back to reference Spitzweg C, Dietz AB, O’Connor MK, et al. (2001) In vivo sodium iodide symporter gene therapy of prostate cancer. Gene Ther 8:1524–1531CrossRefPubMed Spitzweg C, Dietz AB, O’Connor MK, et al. (2001) In vivo sodium iodide symporter gene therapy of prostate cancer. Gene Ther 8:1524–1531CrossRefPubMed
10.
go back to reference Dingli D, Diaz RM, Bergert ER, O’Connor MK, Morris JC, Russell SJ (2003) Genetically targeted radiotherapy for multiple myeloma. Blood 20:20 Dingli D, Diaz RM, Bergert ER, O’Connor MK, Morris JC, Russell SJ (2003) Genetically targeted radiotherapy for multiple myeloma. Blood 20:20
11.
go back to reference Dingli D, Peng KW, Harvey ME, O’Connor MK, Cattaneo R, Morris JC, Russell SJ (2004) Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter. Blood 103:1641–1646CrossRefPubMed Dingli D, Peng KW, Harvey ME, O’Connor MK, Cattaneo R, Morris JC, Russell SJ (2004) Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter. Blood 103:1641–1646CrossRefPubMed
12.
go back to reference Eskandari S, Loo DD, Dai G, Levy O, Wright EM, Carrasco N (1997) Thyroid Na+/Isymporter. Mechanism, stoichiometry, and specificity. J Biol Chem 272:27230–27238CrossRefPubMed Eskandari S, Loo DD, Dai G, Levy O, Wright EM, Carrasco N (1997) Thyroid Na+/Isymporter. Mechanism, stoichiometry, and specificity. J Biol Chem 272:27230–27238CrossRefPubMed
13.
go back to reference Carlin S, Cunningham SH, Boyd M, McCluskey AG, Mairs RJ (2000) Experimental targeted radioiodide therapy following transfection of the sodium iodide symporter gene: Effect on clonogenicity in both two-and three-dimensional models. Cancer Gene Ther 7:1529–1536CrossRefPubMed Carlin S, Cunningham SH, Boyd M, McCluskey AG, Mairs RJ (2000) Experimental targeted radioiodide therapy following transfection of the sodium iodide symporter gene: Effect on clonogenicity in both two-and three-dimensional models. Cancer Gene Ther 7:1529–1536CrossRefPubMed
14.
go back to reference Van Sande J, Massart C, Beauwens R, et al. (2003) Anion selectivity by the sodium iodide symporter. Endocrinology 144:247–252CrossRefPubMed Van Sande J, Massart C, Beauwens R, et al. (2003) Anion selectivity by the sodium iodide symporter. Endocrinology 144:247–252CrossRefPubMed
15.
go back to reference Cho JY, Shen DH, Yang W, et al. (2002) In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas. Gene Ther 9:1139–1145CrossRefPubMed Cho JY, Shen DH, Yang W, et al. (2002) In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas. Gene Ther 9:1139–1145CrossRefPubMed
16.
go back to reference Barton KN, Tyson D, Stricker H, Lew YS, Heisey G, Koul S, de la Zerda A, Yin FF, Yan H, Nagaraja TN, Randall KA, Jin GK, Fenstermacher JD, Jhiang S, Kim JH, Freytag SO, Brown SL (2003) GENIS: Gene expression of sodium iodide symporter for noninvasive imaging of gene therapy vectors and quantification of gene expression in vivo. Molec Ther 8:508–518CrossRef Barton KN, Tyson D, Stricker H, Lew YS, Heisey G, Koul S, de la Zerda A, Yin FF, Yan H, Nagaraja TN, Randall KA, Jin GK, Fenstermacher JD, Jhiang S, Kim JH, Freytag SO, Brown SL (2003) GENIS: Gene expression of sodium iodide symporter for noninvasive imaging of gene therapy vectors and quantification of gene expression in vivo. Molec Ther 8:508–518CrossRef
17.
go back to reference Groot-Wassink T, Aboagye EO, Glaser M, Lemoine NR, Vassaux G (2002) Adenovirus biodistribution and noninvasive imaging of gene expression in vivo by positron emission tomography using human sodium/iodide symporter as reporter gene. Hum Gene Ther 13:1723–1735CrossRefPubMed Groot-Wassink T, Aboagye EO, Glaser M, Lemoine NR, Vassaux G (2002) Adenovirus biodistribution and noninvasive imaging of gene expression in vivo by positron emission tomography using human sodium/iodide symporter as reporter gene. Hum Gene Ther 13:1723–1735CrossRefPubMed
18.
go back to reference Lardinois D, Weder W, Hany TF, Kamel EM, Korom S, Seifert B, von Schulthess GK, Steinert HC (2003) Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 348:2500–2507CrossRefPubMed Lardinois D, Weder W, Hany TF, Kamel EM, Korom S, Seifert B, von Schulthess GK, Steinert HC (2003) Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 348:2500–2507CrossRefPubMed
19.
go back to reference Pentlow KS, Graham MC, Lambrecht RM, Cheung NK, Larson SM (1991) Quantitative imaging of I-124 using positron emission tomography with applications to radioimmunodiagnosis and radioimmunotherapy. Med Phys 18:357–366CrossRefPubMed Pentlow KS, Graham MC, Lambrecht RM, Cheung NK, Larson SM (1991) Quantitative imaging of I-124 using positron emission tomography with applications to radioimmunodiagnosis and radioimmunotherapy. Med Phys 18:357–366CrossRefPubMed
20.
go back to reference Herzog H, Tellmann L, Qaim SM, Spellerberg S, Schmid A, Coenen HH (2002) PET quantitation and imaging of th enon-pure positron-emitting iodine isotope 124I. Appl Radiat Isotopes 56:673–679CrossRef Herzog H, Tellmann L, Qaim SM, Spellerberg S, Schmid A, Coenen HH (2002) PET quantitation and imaging of th enon-pure positron-emitting iodine isotope 124I. Appl Radiat Isotopes 56:673–679CrossRef
21.
go back to reference Jhiang SM, Cho JY, Ryu KY, et al. (1998) An immunohistochemical study of Na+/Isymporter in human thyroid tissues and salivary gland tissues. Endocrinology 139:4416–4419CrossRefPubMed Jhiang SM, Cho JY, Ryu KY, et al. (1998) An immunohistochemical study of Na+/Isymporter in human thyroid tissues and salivary gland tissues. Endocrinology 139:4416–4419CrossRefPubMed
22.
go back to reference Spitzweg C, Joba W, Eisenmenger W, Heufelder AE (1998) Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa. J Clin Endocrinol Metab 83:1746–1751CrossRefPubMed Spitzweg C, Joba W, Eisenmenger W, Heufelder AE (1998) Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa. J Clin Endocrinol Metab 83:1746–1751CrossRefPubMed
23.
go back to reference Spitzweg C, Joba W, Schriever K, Goellner JR, Morris JC, Heufelder AE (1999) Analysis of human sodium iodide symporter immunoreactivity in human exocrine glands. J Clin Endocrinol Metab 84:4178–4184CrossRefPubMed Spitzweg C, Joba W, Schriever K, Goellner JR, Morris JC, Heufelder AE (1999) Analysis of human sodium iodide symporter immunoreactivity in human exocrine glands. J Clin Endocrinol Metab 84:4178–4184CrossRefPubMed
24.
25.
go back to reference Riedel C, Levy O, Carrasco N (2001) Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin. J Biol Chem 276:21458–21463CrossRefPubMed Riedel C, Levy O, Carrasco N (2001) Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin. J Biol Chem 276:21458–21463CrossRefPubMed
26.
go back to reference Radecke F, Spielhofer P, Schneider H, et al. (1995) Rescue of measles viruses from cloned DNA. EMBO J 14:5773–5784PubMed Radecke F, Spielhofer P, Schneider H, et al. (1995) Rescue of measles viruses from cloned DNA. EMBO J 14:5773–5784PubMed
27.
go back to reference Spitzweg C, O’Connor MK, Bergert ER, Tindall DJ, Young CY, Morris JC (2000) Treatment of prostate cancer by radioiodine therapy after tissue- specific expression of the sodium iodide symporter. Cancer Res 60:6526–6530PubMed Spitzweg C, O’Connor MK, Bergert ER, Tindall DJ, Young CY, Morris JC (2000) Treatment of prostate cancer by radioiodine therapy after tissue- specific expression of the sodium iodide symporter. Cancer Res 60:6526–6530PubMed
28.
go back to reference Schneider-Schaulies S, Schneider-Schaulies J, Niewiesk S, Ter Meulen V (2002) Measles virus: Immunomodulation and cell tropism as pathogenicity determinants. Med Microbiol Immunol (Berl) 191:83–87CrossRef Schneider-Schaulies S, Schneider-Schaulies J, Niewiesk S, Ter Meulen V (2002) Measles virus: Immunomodulation and cell tropism as pathogenicity determinants. Med Microbiol Immunol (Berl) 191:83–87CrossRef
29.
go back to reference Groot-Wassink T, Aboagye EO, Wang Y, Lemoine NR, Reader AJ, Vassaux G (2004) Quantitative imaging of Na/I symporter transgene expression using positron emission tomography in the living animal. Molec Ther 9:436–442CrossRef Groot-Wassink T, Aboagye EO, Wang Y, Lemoine NR, Reader AJ, Vassaux G (2004) Quantitative imaging of Na/I symporter transgene expression using positron emission tomography in the living animal. Molec Ther 9:436–442CrossRef
Metadata
Title
Combined I-124 Positron Emission Tomography/Computed Tomography Imaging of NIS Gene Expression in Animal Models of Stably Transfected and Intravenously Transfected Tumor
Authors
David Dingli
Brad J. Kemp
Michael K. O’Connor
John C. Morris
Stephen J. Russell
Val J. Lowe, MD
Publication date
01-01-2006
Publisher
Springer-Verlag
Published in
Molecular Imaging and Biology / Issue 1/2006
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-005-0025-0

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