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Open AccessArticle

Synthesis and Preliminary Biological Evaluations of Fluorescent or 149Promethium Labeled Trastuzumab-Polyethylenimine

by Jonathan Fitzsimmons 1,*,†, Tapan Nayak 2,3,†, Cathy Cutler 4,† and Robert Atcher 1,3
1
Chemistry, Life, and Earth Sciences Directorate, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
2
Department of Cell Biology and Physiology, School of Medicine, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA
3
College of Pharmacy, Radiopharmaceutical Sciences Program, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA
4
University of Missouri Research Reactor (MURR), University of Missouri-Columbia, Columbia MO 65211, USA
*
Author to whom correspondence should be addressed.
Present address: Building 801, Brookhaven National Lab, Upton 11973, NY, USA (J.F. & C.C.); F Hoffmann La Roche, Basel CH 4070, Switzerland (T.N.).
Academic Editor: Michael A. Firer
Biomedicines 2016, 4(1), 1; https://doi.org/10.3390/biomedicines4010001
Received: 12 November 2015 / Revised: 11 December 2015 / Accepted: 15 December 2015 / Published: 30 December 2015
Background: Radioimmunotherapy utilize a targeting antibody coupled to a therapeutic isotope to target and treat a tumor or disease. In this study we examine the synthesis and cell binding of a polymer scaffold containing a radiotherapeutic isotope and a targeting antibody. Methods: The multistep synthesis of a fluorescent or 149Promethium-labeled Trastuzumab-polyethyleneimine (PEI), Trastuzumab, or PEI is described. In vitro uptake, internalization and/or the binding affinity to the Her2/neu expressing human breast adenocarcinoma SKBr3 cells was investigated with the labeled compounds. Results: Fluorescent-labeled Trastuzumab-PEI was internalized more into cells at 2 and 18 h than fluorescent-labeled Trastuzumab or PEI. The fluorescent-labeled Trastuzumab was concentrated on the cell surface at 2 and 18 h and the labeled PEI had minimal uptake. DOTA-PEI was prepared and contained an average of 16 chelates per PEI; the compound was radio-labeled with 149Promethium and conjugated to Trastuzumab. The purified 149Pm-DOTA-PEI-Trastuzumab had a radiochemical purity of 96.7% and a specific activity of 0.118 TBq/g. The compound demonstrated a dissociation constant for the Her2/neu receptor of 20.30 ± 6.91 nM. Conclusion: The results indicate the DOTA-PEI-Trastuzumab compound has potential as a targeted therapeutic carrier, and future in vivo studies should be performed. View Full-Text
Keywords: Promethium-149; Trastuzumab; polyethylenimine; radiotherapy; targeted therapy; Actinium-225 Promethium-149; Trastuzumab; polyethylenimine; radiotherapy; targeted therapy; Actinium-225
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Fitzsimmons, J.; Nayak, T.; Cutler, C.; Atcher, R. Synthesis and Preliminary Biological Evaluations of Fluorescent or 149Promethium Labeled Trastuzumab-Polyethylenimine. Biomedicines 2016, 4, 1.

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