Dynamics of tumor imaging with Gd‐DTPA—polyethylene glycol polymers: Dependence on molecular weight

Abstract

Macromolecular contrast media offer potential advantages over freely diffusible agents in magnetic resonance (MR) imaging outside the central nervous system. To identify an optimum molecular weight for macromolecular contrast media, the authors studied a novel macromolecular contrast agent, gadolinium diethylenetriaminepentaacetic acid polyethylene glycol (DTPA-PEG), synthesized in seven polymer (average) molecular weights ranging from 10 to 83 kd. Twenty-eight rabbits bearing V2 carcinoma in thighs underwent T1-weighted spin-echo imaging before injection and 5-60 minutes and 24 hours after injection of the Gd-DTPA-PEG polymers or Gd-DTPA at a gadolinium dose of 0.1 mmol/kg. Tumor region-of-interest measurements were obtained at each time point to determine contrast enhancement dynamics. Blood-pool enhancement dynamics were observed for the Gd-DTPA-PEG polymers larger than 20 kd. Polymers smaller than 20 kd displayed dynamics similar to those of the freely diffusible agent Gd-DTPA. Above the 20 kd threshold, tumor enhancement was more rapid for smaller polymers. The authors conclude that the 21.9-kd Gd-DTPA-PEG polymer is best suited for clinical MR imaging.

Contrast-enhanced 3D-MRA of the upper abdomen with a bolus-injectable SPIO (SH U 555 A)

“…Another approach is to use protein binding to decrease nonspecific extravasation and to increase the blood-half life of gadolinium-based agents. Earlier blood pool prototypes contained gadolinium chelates irreversibly bound covalently to large polymeric structures (4,8,17,22,23). The most advanced agent in clinical trials is MS-325 (EPIX Medical, Cambridge, MA), which binds reversibly to human serum albumin, providing a primarily vascular distribution and prolonged plasma half-life (7,24).…”

Synthesis, Characterization, and Pharmacokinetic Evaluation of a Potential MRI Contrast Agent Containing Two Paramagnetic Centers with Albumin Binding Affinity

“…[4,5] Although incorporation of paramagnetic compounds into liposomes efficiently increases rotational correlation time, the application of these particles in vivo has some disadvantages, such as their rapid physiological removal by Kupffer cells of the liver and spleen, and their relatively slow clearance rate, which may be harmful to human tissue. [6] An alternative strategy is the synthesis of macromolecular gadolinium(iii) chelates, such as dendrimers, [7] linear polymers, [8][9][10] or proteins. [2,[11][12] This strategy, however, has proved to be rather disappointing, as the relaxivity gained by increasing the molecular size is often much less than expected, because of the internal flexibility or nonrigid attachment of the chelate to the macromolecule.…”

Near‐infrared imaging of breast cancer using optical contrast agents

“…In healthy tissue, the smaller vessel pores preclude extravasation of macromolecules with a molecular weight of approx. 20 kDa or more [99]. ICG was administered over approx.…”