Fluorinated Proteins as Potential 19F Magnetic Resonance Imaging and Spectroscopy Agents

Abstract

Fluorinated proteins have been synthesized and characterized as potential in vivo 19F magnetic resonance imaging (MRI) and spectroscopy (MRS) agents. Proteins labeled with fluorine include bovine serum albumin, gamma-globulin, and purified immunoglobulin (IgG). The amino groups in proteins were selectively trifluoroacetylated using S-ethyl trifluorothioacetate to synthesize fluorinated proteins (TFA-protein; 1-3). In another approach, trifluoroacetamidosuccinic anhydride has been used to prepare corresponding fluorinated derivatives of proteins (TFASA-protein; 4-6). The fluorinated proteins have been purified by exhaustive dialysis and isolated in good yields (55-76%). The fluorinated proteins exhibit useful NMR characteristics and the biocompatibility for in vivo studies. The initial investigations demonstrate the potential of these new fluorinated proteins as in vivo MRI/MRS probes.

6‐Fluoropyridoxol: A novel probe of cellular pH using 19F NMR spectroscopy

“…In addition, the pK, is sensitive to metals ions (e.g. [Mg2']) and ionic strength and errors as great as 0.5 pH units have been estimated [6,17,20,21] -base -1 ppm) [ 10, 23,24], but they have nonetheless been used in isolated cells [lo] and perfused organs [25,26]. Second generation molecules (fluoroanilines) have been described, but exhibited inappropriate PK, U31.…”

Synthesis and Evaluation of Water‐Soluble Fluorinated Dendritic Block‐Copolymer Nanoparticles as a 19F‐MRI Contrast Agent

“…The T 1 relaxation time of PAMAM-g-PTFPMA in methanol was previously reported to be 300 ms. [6] T 1 values were 114, 172, 227, and 244 ms for the four PAMAM-g-PTFPMA-b-PCMB samples of F 3 -b-C1, F 7 -b-C2, F 40 -b-C3, and F 240 -b-C4, respectively. These T 1 values were much shorter than the typical values of T 1 for low-molecular-weight fluorinated compounds, [22][23][24] and consequently allowed us to accumulate the imaging signals with a faster repetition time. On the other hand, in general, high molecular weight compounds have a lower mobility, resulting in a shorter T 2 and broader resonant peak.…”

Design of protein homocystamides with enhanced tumor uptake properties for 19F magnetic resonance imaging

“…In particular, fluorinated proteins have been synthesized by Vimal D. Mehta and coworkers. 33 The amino groups in bovine serum albumin (TFA-albumin) and other proteins were labeled using Sethyl trifluorothioacetate or trifluoroacetamidosuccinic anhydride to prepare corresponding fluorinated derivatives of proteins. The fluorinated proteins were demonstrated to exhibit useful NMR characteristics and also biocompatibility for in vivo studies.…”

“…46 Another approach to protein fluorination is through chemical conjugation of fluorinated anhydrides to the -amino group of a protein lysine residue. 33 However, albumin has a large number of lysine residues (59 for HSA). Therefore, it is very difficult to obtain a single product in the reaction with fluorinated anhydrides.…”