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

Journal Article · Wed Dec 30 00:00:00 EST 2015 · Biomedicines

DOI:https://doi.org/10.3390/biomedicines4010001· OSTI ID:1240731

Fitzsimmons, Jonathan ^[1]; Nayak, Tapan ^[2]; Cutler, Cathy ^[3]; Atcher, Robert ^[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)

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.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: USDOE
• Grant/Contract Number: AC52-06NA25396
• OSTI ID: 1240731
• Report Number(s): LA-UR-16-20619; BIOMID; PII: biomedicines4010001
• Journal Information: Biomedicines, Vol. 4, Issue 1; ISSN 2227-9059
• Publisher: MDPI
• Country of Publication: United States
• Language: English

Related Subjects

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