Polylysine-Gd-DTPAn and Polylysine-Gd-DOTAn Coupled to Anti-CEA F(ab′)2 Fragments as Potential Immunocontrast Agents

Abstract

The immunoreactivity of the gadolinium (Gd)-labeled anti-CEA F(ab')2 immunoconjugates was 80% to 85%. Compared with that of commercial chelates, the relaxivity (R1) increase is as follows: Gd-DTPA < Gd-DOTA < Gd-H2O < PL-Gd-DTPA24-28 < PL-Gd-DTPA24-28 F(ab')2 < PL-Gd-DOTA24-28 < PL-Gd-DOTA24-28 F(ab')2. 1H nuclear magnetic relaxation dispersion data of immunoconjugates showed that the high relaxivity enhancement was the result of a reduction of the molecular tumbling rate. Twenty-four hours after intravenous injection of 50 micrograms (1 mumol Gd/kg) of Gd-labeled immunoconjugates to nude mice grafted with human colorectal carcinoma LS 174T, the tumor uptake was 10% to 15%, resulting in an increase of R1 of up to 15% to 20% versus noninjected mice. No difference was found between PL-Gd-DTPA24-28 F(ab')2 and PL-Gd-DOTA24-28 F(ab')2 immunoconjugates for tumor, liver, and kidney uptake. A high signal intensity of tumor was observed in 50% of the tested mice.

Inulin as a Carrier for Contrast Agents in Magnetic Resonance Imaging

“…[23] This discrepancy in t R value may be accounted for by local rotations of the tether that connects the Gd III chelate to the polymer; these may be more rapid compared with the overall rotation of the conjugate. Similar observations have been reported for macromolecular compounds with Gd III chelates attached to other polymeric carriers, including polylysine, [15,24] polyornithine, [15] dextrans, [16] and dendrimers. [25] As already stated above, the mobility of the tether will decrease upon increase of the ds due to an increase of the steric crowding.…”

Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications

“…304 In this example, paramagnetic loading as high as 24 to 28 metal ions per antibody was obtained without sacrificing immunoreactivity (80-85%) for conjugates PL-Gd-DTPA 24-28 F(ab′) 2 and PL-Gd-DOTA 24-28 F(ab′). The bipohysical data for these conjugates are listed in Table 25.…”

Luminescent and Magnetic Nanoparticulates as Biomarkers

“…Hence the relaxivity of paramagnetic agents is generally enhanced by tuning the various parameters, such as rotational correlation time Tr (tumbling time of CA in water), water proton residence time TM (exchange rate of single inner coordinated water molecule with the bulk water) and electron spin relaxation time Te, related to inner sphere interaction 45) . Relaxivity of the protons associated with inner sphere can be increased by increasing the tumbling time of CA which can be achieved by increasing the effective size of the CA either by using polymer or dendrimer scaffold [46][47][48][49][50][51][52][53] or by conjugating them with slowly tumbling macromolecules 54) . Relaxivity can also be increased by decreasing the TM which depends on the coordination number, charge and geometr y of the paramagnetic CA.…”