Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts

Davide Ricci; Ari A. Mennander; Linh D. Pham; Vinay P. Rao; Naoto Miyagi; Guerard W. Byrne; Stephen J. Russell; Christopher G.A. McGregor

doi:10.1016/j.ejcts.2007.09.033

Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts

Davide Ricci, Ari A. Mennander, Linh D. Pham, Vinay P. Rao, Naoto Miyagi, Guerard W. Byrne, Stephen J. Russell, Christopher G.A. McGregor

Research output: Contribution to journal › Article › peer-review

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Abstract

Objective: We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods: Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 min prior to transplantation with University of Wisconsin (UW) solution (n = 3), with 10⁹ pfu/ml of adenovirus expressing hNIS (Ad-NIS; n = 6), hNIS-hCEA (Ad-NIS-CEA; n = 6) and hNIS-βhCG (Ad-NIS-CG; n = 6). On postoperative day (POD) 5, 10, 15 all animals underwent micro-single photon emission computed tomography/computed tomography (SPECT/CT) imaging of the donor hearts after tail vein injection of 1000 μCi ¹²³I and blood sample collection for hCEA and βhCG quantification. Results: Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1 ± 0.2; 0.9 ± 0.07), Ad-NIS-CEA (1.2 ± 0.3; 0.9 ± 0.1) and Ad-NIS-CG (1.1 ± 0.1; 0.9 ± 0.1) compared to UW group (0.44 ± 0.03; 0.47 ± 0.06) on POD 5 and 10 (p < 0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac ¹²³I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R² = 0.99 and R² = 0.96, respectively). Conclusions: These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic SPECT imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5.

Original language	English (US)
Pages (from-to)	32-39
Number of pages	8
Journal	European Journal of Cardio-thoracic Surgery
Volume	33
Issue number	1
DOIs	https://doi.org/10.1016/j.ejcts.2007.09.033
State	Published - Jan 2008
Externally published	Yes

Bibliographical note

Funding Information:
§Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16—19, 2007. §§ This research is supported by NIH Grant HL66598 and the William J. von Liebig Foundation. * Corresponding author. Address: Mayo Clinic William J von Liebig Transplant Center, 9-233 Charlton Building, Rochester, MN 55905, USA. Tel.: +1 507 255 6038; fax: +1 507 255 4500. E-mail address: mcgregor.christopher@mayo.edu (C.G.A. McGregor).

Keywords

Gene therapy
Heart transplantation
Molecular imaging
Single photon emission computed tomography (SPECT)
Sodium iodide symporter (NIS)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{f273d82fdb574863abe088f7292f88f1,

title = "Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts",

abstract = "Objective: We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods: Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 min prior to transplantation with University of Wisconsin (UW) solution (n = 3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n = 6), hNIS-hCEA (Ad-NIS-CEA; n = 6) and hNIS-βhCG (Ad-NIS-CG; n = 6). On postoperative day (POD) 5, 10, 15 all animals underwent micro-single photon emission computed tomography/computed tomography (SPECT/CT) imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results: Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1 ± 0.2; 0.9 ± 0.07), Ad-NIS-CEA (1.2 ± 0.3; 0.9 ± 0.1) and Ad-NIS-CG (1.1 ± 0.1; 0.9 ± 0.1) compared to UW group (0.44 ± 0.03; 0.47 ± 0.06) on POD 5 and 10 (p < 0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2 = 0.99 and R2 = 0.96, respectively). Conclusions: These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic SPECT imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5.",

keywords = "Gene therapy, Heart transplantation, Molecular imaging, Single photon emission computed tomography (SPECT), Sodium iodide symporter (NIS)",

author = "Davide Ricci and Mennander, {Ari A.} and Pham, {Linh D.} and Rao, {Vinay P.} and Naoto Miyagi and Byrne, {Guerard W.} and Russell, {Stephen J.} and McGregor, {Christopher G.A.}",

note = "Funding Information: §Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16—19, 2007. §§ This research is supported by NIH Grant HL66598 and the William J. von Liebig Foundation. * Corresponding author. Address: Mayo Clinic William J von Liebig Transplant Center, 9-233 Charlton Building, Rochester, MN 55905, USA. Tel.: +1 507 255 6038; fax: +1 507 255 4500. E-mail address: mcgregor.christopher@mayo.edu (C.G.A. McGregor).",

year = "2008",

month = jan,

doi = "10.1016/j.ejcts.2007.09.033",

language = "English (US)",

volume = "33",

pages = "32--39",

journal = "European Journal of Cardio-thoracic Surgery",

issn = "1010-7940",

publisher = "Elsevier",

number = "1",

}

TY - JOUR

T1 - Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts

AU - Ricci, Davide

AU - Mennander, Ari A.

AU - Pham, Linh D.

AU - Rao, Vinay P.

AU - Miyagi, Naoto

AU - Byrne, Guerard W.

AU - Russell, Stephen J.

AU - McGregor, Christopher G.A.

N1 - Funding Information: §Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16—19, 2007. §§ This research is supported by NIH Grant HL66598 and the William J. von Liebig Foundation. * Corresponding author. Address: Mayo Clinic William J von Liebig Transplant Center, 9-233 Charlton Building, Rochester, MN 55905, USA. Tel.: +1 507 255 6038; fax: +1 507 255 4500. E-mail address: mcgregor.christopher@mayo.edu (C.G.A. McGregor).

PY - 2008/1

Y1 - 2008/1

N2 - Objective: We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods: Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 min prior to transplantation with University of Wisconsin (UW) solution (n = 3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n = 6), hNIS-hCEA (Ad-NIS-CEA; n = 6) and hNIS-βhCG (Ad-NIS-CG; n = 6). On postoperative day (POD) 5, 10, 15 all animals underwent micro-single photon emission computed tomography/computed tomography (SPECT/CT) imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results: Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1 ± 0.2; 0.9 ± 0.07), Ad-NIS-CEA (1.2 ± 0.3; 0.9 ± 0.1) and Ad-NIS-CG (1.1 ± 0.1; 0.9 ± 0.1) compared to UW group (0.44 ± 0.03; 0.47 ± 0.06) on POD 5 and 10 (p < 0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2 = 0.99 and R2 = 0.96, respectively). Conclusions: These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic SPECT imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5.

AB - Objective: We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods: Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 min prior to transplantation with University of Wisconsin (UW) solution (n = 3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n = 6), hNIS-hCEA (Ad-NIS-CEA; n = 6) and hNIS-βhCG (Ad-NIS-CG; n = 6). On postoperative day (POD) 5, 10, 15 all animals underwent micro-single photon emission computed tomography/computed tomography (SPECT/CT) imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results: Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1 ± 0.2; 0.9 ± 0.07), Ad-NIS-CEA (1.2 ± 0.3; 0.9 ± 0.1) and Ad-NIS-CG (1.1 ± 0.1; 0.9 ± 0.1) compared to UW group (0.44 ± 0.03; 0.47 ± 0.06) on POD 5 and 10 (p < 0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2 = 0.99 and R2 = 0.96, respectively). Conclusions: These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic SPECT imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5.

KW - Gene therapy

KW - Heart transplantation

KW - Molecular imaging

KW - Single photon emission computed tomography (SPECT)

KW - Sodium iodide symporter (NIS)

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Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts

Abstract

Bibliographical note

Keywords

UN SDGs

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