Preclinical Evaluation and Dosimetry of [
Animals
Antibodies
/ metabolism
Antigens, CD
/ metabolism
Cell Line, Tumor
Disease Models, Animal
Female
Humans
Indium Radioisotopes
/ chemistry
Mice, Inbred BALB C
Neoplasm Proteins
/ metabolism
Radiometry
Radiopharmaceuticals
/ chemistry
Tissue Distribution
Tomography, Emission-Computed, Single-Photon
Tomography, X-Ray Computed
Biodistribution
CD248
Dose extrapolation
Endosialin
Ewing’s sarcoma
Internal dosimetry
Molecular imaging
Neuroblastoma
Radiolabeled scFv78-Fc
TEM1
Journal
Molecular imaging and biology
ISSN: 1860-2002
Titre abrégé: Mol Imaging Biol
Pays: United States
ID NLM: 101125610
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
30
1
2020
medline:
8
7
2021
entrez:
30
1
2020
Statut:
ppublish
Résumé
Endosialin/tumor endothelial marker-1 (TEM1) is an attractive theranostic target expressed by the microenvironment of a wide range of tumors, as well as by sarcoma and neuroblastoma cells. We report on the radiolabeling and preclinical evaluation of the scFv78-Fc, a fully human TEM1-targeting antibody fragment cross-reactive with mouse TEM1. The scFv78-Fc was conjugated with the chelator p-SCN-Bn-CHX-A"-DTPA, followed by labeling with indium-111. The number of chelators per molecule was estimated by mass spectrometry. A conventional saturation assay, extrapolated to infinite antigen concentration, was used to determine the immunoreactive fraction of the radioimmunoconjugate. The radiopharmaceutical biodistribution was assessed in immunodeficient mice grafted with Ewing's sarcoma RD-ES and neuroblastoma SK-N-AS human TEM1-positive tumors. The full biodistribution studies were preceded by a dose-escalation experiment based on the simultaneous administration of the radiopharmaceutical with increasing amounts of unlabeled scFv78-Fc. Radiation dosimetry extrapolations to human adults were obtained from mouse biodistribution data according to established methodologies and additional assumptions concerning the impact of the tumor antigenic sink in the cross-species translation. [ [
Identifiants
pubmed: 31993928
doi: 10.1007/s11307-020-01479-8
pii: 10.1007/s11307-020-01479-8
pmc: PMC7343747
doi:
Substances chimiques
Antibodies
0
Antigens, CD
0
Indium Radioisotopes
0
Neoplasm Proteins
0
Radiopharmaceuticals
0
tumor endothelial marker 1, mouse
0
Indium-111
E9NGC49E0T
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
979-991Commentaires et corrections
Type : ErratumIn
Références
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