title: Evaluation of (111)In labeled antibodies for SPECT imaging of mesothelin expressing tumors.
abstract: BACKGROUND
  Mesothelin is expressed in many cancers, especially in mesothelioma and lung, pancreatic and ovarian cancers. In the present study, we evaluate (111)In labeled antimesothelin antibodies as an imaging bioprobe for the SPECT imaging of mesothelin-expressing tumors.
  
  
  METHODS
  We radiolabeled the antimesothelin antibodies mAbMB and mAbK1 with (111)In using the p-SCN-bn-DTPA chelator. The immunoreactivity, affinity (K(d)) and internalization properties of the resulting two (111)In labeled antibodies were evaluated in vitro using mesothelin-expressing A431K5 cells. The biodistribution and microSPECT/CT imaging studies with (111)In labeled antibodies were performed in mice bearing both mesothelin positive (A431K5) and mesothelin negative (A431) tumors.
  
  
  RESULTS
  In vitro studies demonstrated that (111)In-mAbMB bound with a higher affinity (K(d)=3.6±1.7 nM) to the mesothelin-expressing A431K5 cells than did the (111)In-mAbK1 (K(d)=29.3±2.3 nM). (111)In-mAbMB was also internalized at a greater rate and extent into the A431K5 cells than was the (111)In-mAbK1. Biodistribution studies showed that (111)In-mAbMB was preferentially localized in A431K5 tumors when compared to A431 tumors. At the low dose, the peak A431K5 tumor uptake of 9.65±2.65% ID/g (injected dose per gram) occurred at 48 h, while at high dose tumor uptake peaked with 14.29±6.18% ID/g at 72 h. Non-specific localization of (111)In-mAbMB was mainly observed in spleen.(111)In-mAbK1 also showed superior localization in A431K5 tumors than in A431 tumors, but the peak uptake was only 3.04±0.68% ID/g at 24 h. MicroSPECT/CT studies confirmed better visualization of A431K5 tumors with (111)In-mAbMB, than with (111)In-mAbK1.
  
  
  CONCLUSIONS
  SPECT imaging of mesothelin expressing tumors was demonstrated successfully. Our findings indicate that the antimesothelin antibody mAbMB has the potential to be developed into a diagnostic agent for imaging mesothelin-expressing cancers.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ripen
authors.initials: R
authors.lastname: Misri
authors.forename: Katayoun
authors.initials: K
authors.lastname: Saatchi
authors.forename: Sylvia S W
authors.initials: SS
authors.lastname: Ng
authors.forename: Ujendra
authors.initials: U
authors.lastname: Kumar
authors.forename: Urs O
authors.initials: UO
authors.lastname: Häfeli
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics; D001692:Biological Transport; D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D000090204:Mesothelin; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D055114:X-Ray Microtomography
chemical_list: D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D007205:Indium Radioisotopes; C000715528:Msln protein, mouse; D000090204:Mesothelin