Elemental Bioimaging of Sheep Bone and Articular Cartilage After Single Application of Gadolinium-Based Contrast Agents

BACKGROUND: Gadolinium-based contrast agents (GBCAs) are applied to enhance magnetic resonance imaging. Gadolinium (Gd), a rare earth metal, is used in a chelated form when administered as GBCA to patients. There is an ongoing scientific debate about the clinical significance of Gd retention in tissues after administration of GBCAs. It is known that bone serves as Gd reservoir, but only sparse information on localization of Gd in bone is available. PURPOSE: The aim of this study was to compare Gd tissue concentration and spatial distribution in femoral epiphysis and diaphysis 10 weeks after single-dose injection of linear and macrocyclic GBCAs in a large animal model. MATERIALS AND METHODS: In this prospective animal study, Swiss-Alpine sheep (n = 36; age range, 4-10 years) received a single injection (0.1 mmol/kg) of macrocyclic (gadobutrol, gadoteridol, and gadoterate meglumine), linear (gadodiamide and gadobenate dimeglumine) GBCAs, or saline. Ten weeks after injection, sheep were killed, and femur heads and shafts were harvested. Gadolinium spatial distribution was determined in 1 sample of each treatment group by laser ablation-inductively coupled plasma-mass spectrometry. All bone specimens were analyzed histopathologically. RESULTS: Injection of GBCAs in female Swiss-Alpine sheep (n = 36) resulted in Gd localization at the endosteal and periosteal surface and in a subset of GBCAs additionally at the cement lines and the bone cartilage junction. No histopathological alterations were observed in the investigated tissue specimens. CONCLUSIONS: Ten weeks after single injection of a clinically relevant dose in adult sheep, both linear species of GBCA resulted in considerably higher accumulation than macrocyclic GBCAs. Gadolinium deposits were restricted to distinct bone and cartilage compartments, such as in bone linings, cement lines, and bone cartilage junctions. Tissue histology remained unaffected

Collagen-Specific Molecular Magnetic Resonance Imaging of Prostate Cancer

Constant interactions between tumor cells and the extracellular matrix (ECM) influence the progression of prostate cancer (PCa). One of the key components of the ECM are collagen fibers, since they are responsible for the tissue stiffness, growth, adhesion, proliferation, migration, invasion/metastasis, cell signaling, and immune recruitment of tumor cells. To explore this molecular marker in the content of PCa, we investigated two different tumor volumes (500 mm3 and 1000 mm3) of a xenograft mouse model of PCa with molecular magnetic resonance imaging (MRI) using a collagen-specific probe. For in vivo MRI evaluation, T1-weighted sequences before and after probe administration were analyzed. No significant signal difference between the two tumor volumes could be found. However, we detected a significant difference between the signal intensity of the peripheral tumor area and the central area of the tumor, at both 500 mm3 (p n = 16) and at 1000 mm3 (p n = 16). The results of our histologic analyses confirmed the in vivo studies: There was no significant difference in the amount of collagen between the two tumor volumes (p > 0.05), but within the tumor, higher collagen expression was observed in the peripheral area compared with the central area of the tumor. Laser ablation with inductively coupled plasma mass spectrometry further confirmed these results. The 1000 mm3 tumors contained 2.8 ± 1.0% collagen and the 500 mm3 tumors contained 3.2 ± 1.2% (n = 16). There was a strong correlation between the in vivo MRI data and the ex vivo histological data (y = −0.068x + 1.1; R2 = 0.74) (n = 16). The results of elemental analysis by inductively coupled plasma mass spectrometry supported the MRI data (y = 3.82x + 0.56; R2 = 0.79; n = 7). MRI with the collagen-specific probe in PCa enables differentiation between different tumor areas. This may help to differentiate tumor from healthy tissue, potentially identifying tumor areas with a specific tumor biology