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: 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.affiliation: Mayo Clinic William J von Liebig Transplant Center, Rochester, MN 55905, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Ricci
authors.forename: Ari A
authors.initials: AA
authors.lastname: Mennander
authors.forename: Linh D
authors.initials: LD
authors.lastname: Pham
authors.forename: Vinay P
authors.initials: VP
authors.lastname: Rao
authors.forename: Naoto
authors.initials: N
authors.lastname: Miyagi
authors.forename: Guerard W
authors.initials: GW
authors.lastname: Byrne
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Christopher G A
authors.initials: CG
authors.lastname: McGregor
mesh_terms: 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
chemical_list: D002272:Carcinoembryonic Antigen; D006063:Chorionic Gonadotropin; D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters