Macrophage CD206 Receptor Targeting with ^sup 99m^ Tc-Tilmanocept Permits Specific Quantitative Diagnostic Imaging of Active Rheumatoid Arthritis (RA) and id Differentiated from Osteoarthritis (OA)

• Published in: The Journal of nuclear medicine (1978) Vol. 58; p. 303
• Main Authors: Abbruzzese, Bonnie, Zubal, George, Behr, Spencer, Ralph, David, Shuping, Joanna, Colborn, David, Kissling, Allison, Sanders, James, DeMeo, Diana, Hartings, Carley, Hershey, Rachel, Blue, Michael, Metz, Wendy, Bailey, Hannah, Springer, Brandon, Spaulding, Amelia, Cope, Frederick
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.05.2017
• Subjects: Arthritis; Background radiation; Biocompatibility; Biopsy; Cells; Computed tomography; Correlation analysis; Damage detection; Diagnostic systems; Image acquisition; Immunomodulation; Infiltration; Injection; Joint diseases; Localization; Macrophages; Medical diagnosis; Medical imaging; Nuclear medicine; Osteoarthritis; Prescription drugs; Quantitative analysis; Radioactivity; Radiology; Rheumatoid arthritis; Rheumatology; Single photon emission computed tomography; Symptomology
• ISSN: 0161-5505; 1535-5667

Objectives: Macrophages play a critical role in rheumatoid arthritis (RA) disease progression, but existing strategies for imaging disease progression in humans lack macrophage and overall disease specificity. We investigated systemic administration of 99mTc-tilmanocept, which specifically binds CD206+ macrophages, to image rheumatoid inflammation and quantify macrophage infiltration in an index population of healthy (non-RA) and RA subjects with clinical RA. Additionally we sought to quantify 99mTc-tilmanocept localization with standard RA scoring devices. The primary objective was to determine the localization of 99mTc-tilmanocept by planar and SPECT/CT imaging in subjects with active RA and concordance with clinical symptomology (DAS28). Secondarily, we a] compared localization intensity between the dose groups of 99mTc-tilmanocept by planar and SPECT/CT imaging; b] evaluated and contrasted localization in subjects with active RA vs subjects who are clinically negative for inflammatory disease(s) by planar and SPECT/CT imaging; c] evaluated areas of localization other than RA affected joints of 99mTc-tilmanocept by planar and SPECT/CT imaging. Methods: a] Prospective, open-label, multicenter, study of 99mTc-tilmanocept in the localization of RA affected joint(s). Subjects received a SC injection of either 50μg tilmanocept or 200μg tilmanocept radiolabeled with 2mCi 99mTc in 0.4mL. 18 subjects were enrolled as follows - Cohort 1: Controls: 50μg/2mCi; n = up to 4; Cohort 2: Controls: 200μg/2mCi; n = up to 4; Cohort 3: RA 50μg/2mCi; n = 5; Cohort 4: RA 200μg/2mCi; n = 5. Subjects were imaged with a whole body planar scan at 2-3 hours and 4-6 hours post injection. After each whole body scan, a separate 5 minute planar image of both hands was acquired. If there were an area showing localization, SPECT/CT images were obtained. b] Localization by 99mTc-tilmanocept was defined as accumulation of radioactivity at an intensity greater than background. Regions of interest as these are represented by DAS28 scoring and correlation with DAS28 were also conducted. Results: High-level 99mTc-tilmanocept uptake was readily visible and detectable across RA affected joints. Preliminary correlation scoring with DAS28 shows that in large affected joints, localization of 99mTc-tilmanocept is significant. The overall initial scoring relative to the DAS28 suggests that localization of 99mTc-tilmanocept in these regions of interest (ROI) has a strong correlation in large joints. Final correlates with smaller joints and full quantitative assessment remain to be completed. Based on these data and prior biopsy evaluations the data suggest that the level of inflammation is strongly related to macrophage infiltration and ultimately image signal (SEE Figure 1). Conclusion: Our findings represent a potentially significant advance in functional imaging of RA utilizing a novel macrophage-specific molecular imaging strategy in humans to quantify RA macrophage infiltration in relationship to clinical symptomology and immune indices in at-risk populations. This strategy may be useful to provide insights into immune-mediated mechanisms of RA, identify patients at risk for macrophage-mediated end joint damage, and enable future targeted delivery of immunomodulatory therapeutics. SC administration of tilmanocept is localized within RA joints. Research Support: Supported NIH/NIAMS grant AR067583-01A1; Listed in ClinicalTrials.gov - NCT02683421. The following were major contributors and due to their absence at the time of the submission, they should be considered authors: Miguel Pampaloni, MD PhD, UCSF-Radiology; Jonathan Graf, MD PhD, UCSF-Rheumatology