title: In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.
abstract: The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody (99m)Tc-D10 for visualizing small tumour lesions with volumes below 100 mm(3) by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody (99m)Tc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm(3) ± 21.2 and 26.6 mm(3) ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of (99m)Tc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody (99m)Tc-D10.
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krüwel
authors.affiliation: Antibody therapeutics and Immunotargeting, CRCM, Inserm U1068, Institut PaoliCalmettes, Aix-Marseille Université UM 105, CNRS UMR7258, F-13009, Marseille, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Nevoltris
authors.affiliation: Molecular Mechanisms of Tumour Cell Invasion (V077), German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bode
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Dullin
authors.affiliation: Antibody therapeutics and Immunotargeting, CRCM, Inserm U1068, Institut PaoliCalmettes, Aix-Marseille Université UM 105, CNRS UMR7258, F-13009, Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Baty
authors.affiliation: Antibody therapeutics and Immunotargeting, CRCM, Inserm U1068, Institut PaoliCalmettes, Aix-Marseille Université UM 105, CNRS UMR7258, F-13009, Marseille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chames
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany.|Department of Haematology and Medical Oncology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany.|Molecular Biology of Neuronal Signals, Max-Planck-Institute for Experimental Medicine, Hermann-Rein-Str. 3, 37075 Goettingen, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Alves
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics*; D061905:Single-Domain Antibodies / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: C000613052:99m Tc-D10 nonobody; D005456:Fluorescent Dyes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D061905:Single-Domain Antibodies; D013667:Technetium; D066246:ErbB Receptors; D000068818:Cetuximab