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Title: Synthesis and preliminary biological evaluations of fluorescent or 149Promethium labeled Trastuzumab-polyethylenimine

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. 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. In conclusion, the results indicate the DOTA-PEI-Trastuzumab compound has potential as a targeted therapeutic carrier, and future in vivo studies should be performed.
Authors:
 [1] ;  [2] ;  [3] ;  [4]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Univ. of New Mexico Health Science Center, Albuquerque, NM (United States)
  3. Univ. of Missouri-Columbia, Columbia, MO (United States)
  4. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of New Mexico Health Science Center, Albuquerque, NM (United States)
Publication Date:
OSTI Identifier:
1240731
Report Number(s):
LA-UR--16-20619
Journal ID: ISSN 2227-9059; BIOMID; PII: biomedicines4010001
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Biomedicines
Additional Journal Information:
Journal Volume: 4; Journal Issue: 1; Journal ID: ISSN 2227-9059
Publisher:
MDPI
Research Org:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 07 ISOTOPE AND RADIATION SOURCES; 77 NANOSCIENCE AND NANOTECHNOLOGY; 38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; 62 RADIOLOGY AND NUCLEAR MEDICINE Promethium-149; Trastuzumab; polyethylenimine; radiotherapy; targeted therapy; Actinium-225