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Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts.
Eur J Cardiothorac Surg 2008; 33(1):32-9EJ

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: betahCG) 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 10(9) pfu/ml of adenovirus expressing hNIS (Ad-NIS; n=6), hNIS-hCEA (Ad-NIS-CEA; n=6) and hNIS-betahCG (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 microCi (123)I and blood sample collection for hCEA and betahCG 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 betahCG increased in animals showing high cardiac (123)I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and betahCG (R(2)=0.99 and R(2)=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.

Authors+Show Affiliations

Mayo Clinic William J von Liebig Transplant Center, Rochester, MN 55905, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17980613

Citation

Ricci, Davide, et al. "Non-invasive Radioiodine Imaging for Accurate Quantitation of NIS Reporter Gene Expression in Transplanted Hearts." European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, vol. 33, no. 1, 2008, pp. 32-9.
Ricci D, Mennander AA, Pham LD, et al. Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts. Eur J Cardiothorac Surg. 2008;33(1):32-9.
Ricci, D., Mennander, A. A., Pham, L. D., Rao, V. P., Miyagi, N., Byrne, G. W., ... McGregor, C. G. (2008). Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts. European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, 33(1), pp. 32-9.
Ricci D, et al. Non-invasive Radioiodine Imaging for Accurate Quantitation of NIS Reporter Gene Expression in Transplanted Hearts. Eur J Cardiothorac Surg. 2008;33(1):32-9. PubMed PMID: 17980613.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2007/11/05/ PY - 2007/07/10/received PY - 2007/09/06/revised PY - 2007/09/10/accepted PY - 2007/11/6/pubmed PY - 2008/8/5/medline PY - 2007/11/6/entrez SP - 32 EP - 9 JF - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery JO - Eur J Cardiothorac Surg VL - 33 IS - 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: betahCG) 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 10(9) pfu/ml of adenovirus expressing hNIS (Ad-NIS; n=6), hNIS-hCEA (Ad-NIS-CEA; n=6) and hNIS-betahCG (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 microCi (123)I and blood sample collection for hCEA and betahCG 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 betahCG increased in animals showing high cardiac (123)I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and betahCG (R(2)=0.99 and R(2)=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. SN - 1010-7940 UR - https://www.unboundmedicine.com/medline/citation/17980613/Non_invasive_radioiodine_imaging_for_accurate_quantitation_of_NIS_reporter_gene_expression_in_transplanted_hearts_ L2 - https://academic.oup.com/ejcts/article-lookup/doi/10.1016/j.ejcts.2007.09.033 DB - PRIME DP - Unbound Medicine ER -