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Biomedicines 2016, 4(1), 1; doi:10.3390/biomedicines4010001

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

Chemistry, Life, and Earth Sciences Directorate, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
Department of Cell Biology and Physiology, School of Medicine, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA
College of Pharmacy, Radiopharmaceutical Sciences Program, University of New Mexico Health Science Center, Albuquerque, NM 87131, USA
University of Missouri Research Reactor (MURR), University of Missouri-Columbia, Columbia MO 65211, USA
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.).
Author to whom correspondence should be addressed.
Academic Editor: Michael A. Firer
Received: 12 November 2015 / Revised: 11 December 2015 / Accepted: 15 December 2015 / Published: 30 December 2015
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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

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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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