Abstract
Background
Anti-tumour necrosis factor antagonists (infliximab) as well as other molecules with different modes of action, including anti-integrin agents (vedolizumab), are currently used in patients with ulcerative colitis (UC Numerous studies have demonstrated a positive correlation between serum biologic drug concentrations and favourable therapeutic outcomes, whereas low or undetectable drug concentrations can lead to treatment failure. However, despite immunological issues, lack of and or loss of response may also be attributed to drug pharmacokinetics, of which penetration to the target tissue (colon wall) may play a crucial role
Methods
We used MRI to perform biochemical analyses of infliximab, adalimumab and vedolizumab concentrations testing the hypothesis that MRI relaxation time can be used to track antibodies in both mucosal biopsy samples and serum. All MR scans were performed with an Optima MR360 from General Electric Healthcare. To determine spin–lattice (T1) and spin–spin (T2) relaxation times, the Fast Spin Echo (FSE) sequence was used.
Results
The measured values of T1 relaxation times for infliximab, adalimumab, and vedolizumab were 2227 ± 35 ms, 2000 ± 22 ms and 1288 ± 15 ms, respectively. The obtained T2 relaxation times were 130 ± 11 ms, 90 ± 5, and 75 ± 10 ms, respectively. A decrease of both T1 and T2 values of 15 ± 3% are observed in serum from patients with ulcerative colitis. The values of infliximab and adalimumab were similar; the values of vedolizumab measurements in serum were about 50% lower. We find primary evidence that in T1 and T2 decreased in serum samples with ulcerative colitis and increase with the administration of infliximab, adalimumab and vedolizumab drugs. Samples of healthy tissue have T1 and T2 in the range of 2700 ± 5 ms and 150 ms ± 5 ms, respectively. A 30% decrease in T1 and T2 are observed for samples with ulcerative colitis. In this pilot study, we observed that values of T1 and T2 for tissues and serum that contain infliximab and adalimumab are similar, but vedolizumab shows a difference of about 30% when compared with infliximab and adalimumab.
Conclusion
MRI is an excellent method for quantitative and qualitative measurements of drug content in tissues and biological fluids. This is an innovative use of magnetic resonance imaging to develop a methodology for imaging of drugs that act as contrast agents via interaction with water in serum and tissue.
The influences of different spatial resolutions on the characteristics of T2 relaxation times in articular cartilage: A coarse-graining study of the microscopic magnetic resonance imaging data
