Toxicity and pharmacokinetic profile of SGM-101, a fluorescent anti-CEA chimeric antibody for fluorescence imaging of tumors in patients - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Toxicology Reports Année : 2019

Toxicity and pharmacokinetic profile of SGM-101, a fluorescent anti-CEA chimeric antibody for fluorescence imaging of tumors in patients

Résumé

The real-time improvement of the intraoperative discrimination between different tissue types (particularly between tumor and adjacent normal tissue) using intraoperative imaging represents a considerable advance for oncology surgeons. However, the development of imaging agents is much slower than that of drug therapies, although surgery represents one of the few curative treatments for many solid tumors. SGM-101 is a recently described, innovative antibody conjugate in which the near-infrared fluorochrome BM-104 is covalently linked to a chimeric monoclonal antibody against carcinoembryonic antigen (CEA). SGM-101 was developed with the goal of providing oncology surgeons with an intraoperative imaging tool that allows the visualization of CEA-overexpressing tumors. This antigen is overexpressed in a wide range of human carcinomas, such as colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Here we characterized SGM-101 safety prior to its clinical testing for real-time cancer mapping by oncology surgeons. Safety pharmacology and toxicology studies were performed after intravenous injection of SGM-101 in Wistar rats and in Beagle dogs. SGM-101 metabolism and pharmacokinetics were analyzed in rats and mice. Finally, the potential toxicity of the BM-104 dye and SGM-101 cross-reactivity were assessed in a panel of 42 human tissues. Our pre-clinical toxicology, pharmacology and pharmacokinetic results demonstrated the absence of significant adverse effects of both SGM-101 and BM-104 at doses well above the anticipated maximal human exposure. Taken together, the results of the pharmacology, pharmacokinetic and toxicology studies support the development of SGM-101 as a potentially useful and safe tumor-specific imaging tool that might improve the complete tumor resection rate.
Fichier principal
Vignette du fichier
1-s2.0-S2214750018306826-main.pdf (411.98 Ko) Télécharger le fichier
Origine Publication financée par une institution
Loading...

Dates et versions

hal-02931825 , version 1 (07-09-2020)

Identifiants

Citer

Bérénice Framery, Marian Gutowski, Karen Dumas, Alexandre Evrard, Nathalie Muller, et al.. Toxicity and pharmacokinetic profile of SGM-101, a fluorescent anti-CEA chimeric antibody for fluorescence imaging of tumors in patients. Toxicology Reports, 2019, 6, pp.409--415. ⟨10.1016/j.toxrep.2019.04.011⟩. ⟨hal-02931825⟩
69 Consultations
100 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More