Click-mediated pretargeted radioimmunotherapy of colorectal carcinoma Journal Article

Authors: Membreno, R.; Cook, B. E.; Fung, K.; Lewis, J. S.; Zeglis, B. M.
Article Title: Click-mediated pretargeted radioimmunotherapy of colorectal carcinoma
Abstract: Pretargeted radioimmunotherapy (PRIT) based on the inverse electron demand Diels-Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) represents a promising strategy for leveraging the affinity and specificity of antibodies without their pharmacokinetic drawbacks. Herein, we present an investigation of the in vivo efficacy and dosimetry of a PRIT strategy for colorectal carcinoma based on the ligation between a 177Lu-labeled Tz radioligand (177Lu-DOTA-PEG7-Tz) and a TCO-bearing immunoconjugate of the huA33 antibody (huA33-TCO). Biodistribution studies in tumor-bearing mice using intervals of 24, 48, and 72 h between the administration of huA33-TCO and 177Lu-DOTA-PEG7-Tz revealed that a 24 h lag time produced the most promising in vivo results: high activity concentrations in the tumor (21.2 %ID/g ± 2.9 at 24 h postinjection), low uptake in nontarget tissues, and favorable dosimetry (an effective dose of 0.054 mSv/MBq). A subsequent longitudinal therapy study revealed striking differences between both the survival and tumor growth of the treatment and control cohorts, clearly underscoring the promise of this approach for the radiotherapy of colorectal carcinoma. © 2018 American Chemical Society.
Keywords: colorectal cancer; radioimmunotherapy; click chemistry; pretargeted radioimmunotherapy; pretargeting; tetrazine; lu-177; trans-cyclooctene; inverse electron demand diels-alder reaction
Journal Title: Molecular Pharmaceutics
Volume: 15
Issue: 4
ISSN: 1543-8384
Publisher: American Chemical Society  
Date Published: 2018-04-02
Start Page: 1729
End Page: 1734
Language: English
DOI: 10.1021/acs.molpharmaceut.8b00093
PROVIDER: scopus
PUBMED: 29502416
PMCID: PMC6467224
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Brian Zeglis
    88 Zeglis
  2. Jason S Lewis
    365 Lewis
  3. Brendon Ellery Cook
    7 Cook