Oxford BioMedica PLC (OXBDF)

[georgejjl]

Pfizer is still interested in 5T4.

Biodistribution and Targeting of Anti-5T4 Antibody-Drug Conjugate Using Fluorescence Molecular Tomography.
Giddabasappa A1, Gupta VR2, Norberg R2, Gupta P2, Spilker ME3, Wentland J4, Rago B4, Eswaraka J2, Leal M5, Sapra P6.
Author information
1Global Science & Technology - Comparative Medicine, Pfizer Inc., San Diego, California. [e-mail].
2Global Science & Technology - Comparative Medicine, Pfizer Inc., San Diego, California.
3Pharmacokinetics Dynamics and Metabolism, Pfizer Inc., San Diego, California.
4Pharmacokinetics Dynamics and Metabolism, Pfizer Inc., Groton, Connecticut.
5Pharmacokinetics Dynamics and Metabolism, Pfizer Inc., Pearl River, New York.
6Oncology Research Unit, Pfizer Inc., Pearl River, New York.
Abstract
Understanding a drug's whole-body biodistribution and tumor targeting can provide important information regarding efficacy, safety, and dosing parameters. Current methods to evaluate biodistribution include in vivo imaging technologies like positron electron tomography and single-photon emission computed tomography or ex vivo quantitation of drug concentrations in tissues using autoradiography and standard biochemical assays. These methods use radioactive compounds or are cumbersome and do not give whole-body information. Here, for the first time, we show the utility of fluorescence molecular tomography (FMT) imaging to determine the biodistribution and targeting of an antibody-drug conjugate (ADC). An anti-5T4-antibody (5T4-Ab) and 5T4-ADC were conjugated with a near-infrared (NIR) fluorophore VivoTag 680XL (VT680). Both conjugated compounds were stable as determined by SEC-HPLC and plasma stability studies. Flow cytometry and fluorescence microscopy studies showed that VT680-conjugated 5T4-ADC specifically bound 5T4-expressing cells in vitro and also exhibited a similar cytotoxicity profile as the unconjugated 5T4-ADC. In vivo biodistribution and tumor targeting in an H1975 subcutaneous xenograft model demonstrated no significant differences between accumulation of VT680-conjugated 5T4-Ab or 5T4-ADC in either normal tissues or tumor. In addition, quantitation of heart signal from FMT imaging showed good correlation with the plasma pharmacokinetic profile suggesting that it (heart FMT imaging) may be a surrogate for plasma drug clearance. These results demonstrate that conjugation of VT680 to 5T4-Ab or 5T4-ADC does not change the behavior of native biologic, and FMT imaging can be a useful tool to understand biodistribution and tumor-targeting kinetics of antibodies, ADCs, and other biologics.

http://www.ncbi.nlm.nih.gov/pubmed/27466353

Good luck and GOD bless,

George