Non-invasive radioiodine imaging for accurate quantitation of NIS reporter gene expression in transplanted hearts.
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.
Ricci
Davide
D
Mayo Clinic William J von Liebig Transplant Center, Rochester, MN 55905, USA.
Mennander
Ari A
AA
Pham
Linh D
LD
Rao
Vinay P
VP
Miyagi
Naoto
N
Byrne
Guerard W
GW
Russell
Stephen J
SJ
McGregor
Christopher G A
CG
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics*; D017930:Genes, Reporter; D016027:Heart Transplantation / Q000000981:diagnostic imaging*; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D016896:Treatment Outcome; D000099209:Sodium-Iodide Symporters
D002272:Carcinoembryonic Antigen; D006063:Chorionic Gonadotropin; D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters