MR imaging of antigen‐induced arthritis with a new, folate receptor‐targeted contrast agent

Abstract

The purpose of this study was to investigate if the new folate receptor-targeted Gd-chelate P866 may enhance immune-mediated arthritis. A monoarthritis was induced in the right knee of 15 Sprague-Dawley rats. MR imaging of both knees was performed at 2 T before and up to 2 h and 24 h after injection (p.i.) of P866 (n = 3 dose finding study and n = 6, 0.02 mmol Gd/kg), the non-FR targeted P866 analog P1001 (n = 3 at 24 h after P866-administration, 0.02 mmol Gd/kg) or Gd-DOTA (n = 6, 0.1 mmol Gd/kg). Pulse sequences comprised T(1)-SPGR 80 degrees /50 ms/1.7 ms (flip angle/TR/TE) and inversion recovery 10 degrees /3000 ms/1500 ms/50-3050, 10 000 ms (flip angle/TR/TE/TI) sequences. DeltaSI-data and T(1)-relaxation times of arthritic knees and contralateral normal knees were determined. Folate receptor expression was confirmed with histopathology. All three contrast agents showed an initial perfusion effect with significantly higher DeltaSI-data of arthritic knees compared with normal knees (p < 0.05). In addition, P866, but not P1001 or Gd-DOTA, showed a prolonged enhancement of the synovitis. Compared with precontrast values, the T(1)-relaxation times of inflamed synovia were significantly decreased at 2 h p.i. of P866 (p < 0.05), but not P1001 or Gd-DOTA (p > 0.05). Histopathology confirmed the presence of folate receptors in the inflamed joints, but not normal joints. Thus, results suggest a specific accumulation of the folate receptor-targeted Gd-chelate P866 in this arthritis model.

Ferumoxytol: A New, Clinically Applicable Label for Stem-Cell Tracking in Arthritic Joints with MRI

“…This study’s group and others have reported that stem cells, labeled with clinically approved gadolinium chelates, can be tracked in arthritic joints [64,65]. Thus, gadolinium labeling would represent a potential alternative to ferumoxytol labeling.…”

Dynamic Contrast-Enhanced Folate-Receptor-Targeted MR Imaging Using a Gd-loaded PEG-Dendrimer–Folate Conjugate in a Mouse Xenograft Tumor Model

“…In the pilot study, we tried to apply conventional postcontrast T1 MR images and compared the enhancement ratio of the FR-positive and -negative tumors at various time points (4,8,12, and 24 h...) after contrast injection, as other authors did in previous receptor-targeted MR studies [15,30]. However, we found that it was difficult to get exactly the same imaging plane of the tumors once we re-arranged the mouse position and the baseline MR signal intensity fluctuated at various time points due to MR unit internal variability.…”

“…In previous receptor-targeted magnetic resonance (MR) imaging studies, authors usually compared the contrast enhancement ratio between the receptor-positive and the -negative tumors at various time points after contrast injection, and showed that the receptor-positive tumors had higher enhancement ratios and longer enhancement durations [12][13][14][15][16][17][18]. However, it is sometimes hard to scan exactly the same cross-sectional area before, and at different time points after contrast injection; thus, it is hard to get unbiased hemodynamic information from a certain portion of the tumor.…”

Inorganic nanoparticle-based contrast agents for molecular imaging

“…A summary of the targeting ligands that have been examined for cancer detection is presented in Table 3 [21, 27, 52–54, 86–104]. Ideally, the targeting ligand should bind exclusively to a receptor on a specific type of cancer cell.…”