MR Imaging of a Paramagnetic HPMA Conjugate for Bone Delivery

Kopecek and coworkers labeled HPMA copolymers (55 kDa) with Gd-DOTA to noninvasively evaluate macromolecular accumulation in arthritic joints in a rat model. The copolymers were labeled with fluorescein in addition to the paramagnetic metal chelate. The structure of the conjugate is shown in Figure 11.3. After intravenous administration of the conjugate in a rat model with adjuvant-induced arthritis, the biodistribution of copolymers was followed by contrast-enhanced MRI at various time points post-injection.35

Contrast-enhanced dynamic MRI clearly revealed the pharmacokinetic properties and biodistribution of the conjugate with high anatomic resolution in the adjuvant-induced arthritic rats (Figure 11.4). The copolymers had a relatively high molecular weight and a considerable amount of the copolymers was still circulating in the blood 3 h post-injection. Selective accumulation of HPMA copolymers was gradually shown in the arthritic joints of the adjuvant-induced arthritis rats. The copolymers were also cleared from the accumulation sites over time as shown by contrast-enhanced MRI. The uptake and retention of the MR contrast agent labeled polymer correlated well with the histopathological features of inflammation and local tissue damages. No significant contrast enhancement was observed in the hind-limb joints of healthy rats in a control study.

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