title: In vivo and in vitro uptake of 111In, delivered with the affibody molecule (ZEGFR:955)2, in EGFR expressing tumour cells.
abstract: The epidermal growth factor receptor, EGFR, is overexpressed in many carcinomas. Targeting this receptor with radionuclides is important for imaging and therapy applications in nuclear medicine. We investigated the in vitro and in vivo properties of a new high affinity EGFR binding affibody molecule, (ZEGFR:955)2, when conjugated with CHX-A''-DTPA and labelled with 111In. The binding time patterns and retention studies were performed using cultured squamous carcinoma A431 cells that overexpress EGFR. In the in vivo studies, female BALB/c nu/nu mice carrying tumours from xenografted A431 cells were used. The in vitro studies showed EGFR specific binding, high uptake and good retention of 111In when delivered as [111In](ZEGFR:955)2. The retention after 72 h of incubation was 38.0+/-1.15% of the initial level. The biodistribution study showed a tumour specific 111In uptake of 3.8+/-1.4% of injected dose per gram tumour tissue 4 h post-injection. The tumour to blood ratio was 9.1 and the tumours could easily be visualized with a gamma camera at this time-point. 111In delivered with [111In](ZEGFR:955)2 gave an EGFR specific uptake and the results indicated that the (ZEGFR:955)2 affibody molecule is a candidate for radionuclide-based tumour imaging. Potential therapy applications are discussed.
authors: Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden. erika.nordberg@bms.uu.se
authors: E
authors: E
authors: Nordberg
authors: A
authors: A
authors: Orlova
authors: M
authors: M
authors: Friedman
authors: V
authors: V
authors: Tolmachev
authors: S
authors: S
authors: Ståhl
authors: F Y
authors: FY
authors: Nilsson
authors: B
authors: B
authors: Glimelius
authors: J
authors: J
authors: Carlsson
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D017879:Isothiocyanates / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism*; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D007205:Indium Radioisotopes; D017879:Isothiocyanates; D019275:Radiopharmaceuticals; C085678:N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid; D004369:Pentetic Acid; D066246:ErbB Receptors