Interesting research - ties into something else related to macrophages and arterial inflammation - new imaging technique for arterial plaque using NAVB's Lymphoseek diagnostic - I've mentioned before that HIV patients would greatly benefit from taking V:
Quantification of Arterial Wall Macrophage Infiltration
CD206+ Macrophage-Specific Molecular Imaging Probe, 99mTc-Tilmanocept, and the Noninvasive Quantification of Arterial Wall Macrophage Infiltration in Humans”
Zanni MV1 , Toribio M1 , Wilks M3 , Lu MT2 , Burdo TH5 , Walker J4 , Foldyna B2 , Stone L1 , Martin A1 , Cope F6 , Abbruzzeze B6 , Brady T3 , Hoffmann U2 , Williams KC4 , El-Fakhri G3 , Grinspoon SK1
Supported by National Institutes of Health (NIH) grants M01-RR-01066 and 1 UL1 RR025758-01 to the Harvard Clinical and Translational Science Center from the National Center for Research Resources. Support was also received from NIH DKP30 045061. Supported in part by a NIH Medical Research Investigator Training Award 8KL2TR000168- 05 and by T32DK 007028. Navidea Biopharmaceuticals received a SBIR Grant 1 R43 HL127846-01 to support the study. 1 Program in Nutritional Metabolism, Mass General Hospital and Harvard Medical School, Boston, MA 2 Cardiac-Magnetic Resonance-Positron Emission Tomography Computed Tomography Program, Division of Radiology, Mass General Hospital and Harvard Medical School, Boston, MA 3 Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Mass General Hospital and Harvard Medical School, Boston, MA; 4 Biology Department, Boston College, Chestnut Hill MA; 5 Dept of Neuroscience, Temple Univ. School of Medicine, Philadelphia, PA; 6 Navidea Biopharmaceuticals, Dublin, OH
Objectives: Macrophages play a critical role in atherosclerotic plaque progression, but existing strategies for imaging arterial inflammation in humans lack macrophage specificity. We investigated systemic administration of 99mTctilmanocept, which specifically binds CD206+ macrophages, to image arterial inflammation and quantify macrophage infiltration in an index population of HIV-infected subjects with subclinical atherosclerosis.
Methods: a] The primary aim of this study was to determine whether in vivo quantification of CD206+ aortic macrophage infiltration in humans could be accomplished non-invasively by thoracic single photon emission computed tomography (SPECT)/CT scanning following subcutaneous administration of 99mTc-tilmanocept. To contextualize the clinical significance of aortic 99mTc-tilmanocept uptake, two additional non-invasive cardiovascular imaging tests were performed - computed tomography angiography (CTA) and 18F-NaF-PET/CT scanning. Moreover, facilitating the identification of clinical parameters relating to aortic 99mTc-tilmanocept uptake, subjects underwent detailed history and blood testing for metabolic markers and markers of systemic immune activation/inflammation. Initially, for the proof-of-concept phase of the study, 6 HIV-infected subjects with known subclinical atherosclerosis based on prior CTA were recruited and enrolled. Subsequently, for comparison, 3 non-HIV-infected subjects matched on Framingham Risk Score were recruited and enrolled. None of the subjects in either group had known current or prior clinical cardiovascular disease. The study, which began in August 2015 and was completed in April 2016, was approved by the Massachusetts General Hospital (MGH) Human Research Committee Institutional Review Board (IRB) and all subjects provided written informed consent. The study was registered on clinicaltrials.gov (NCT02542371). b] For both groups of study subjects (HIV-infected and non-HIV-infected), entry criteria included age ≥ 18 years. Exclusion criteria included history of myocardial infarction, stable or unstable angina, or coronary artery stenting or surgery; current treatment with prescription systemic steroids or anti-inflammatory/immune suppressant medical therapies; any recent treatment with statin therapy.
Results: High-level 99mTc-tilmanocept uptake was readily visible and detectable across 20.4% of the aortic surface volume among HIV-infected subjects compared to only 4.3% in a control population with similar CVD risk indices (P=0.009). Among all subjects, high-level aortic 99mTc-tilmanocept uptake related to total aortic plaque volume and the volume of non-calcified plaque (r = 0.78, P= 0.01). Moreover, 99mTc-tilmanocept uptake was robustly related to circulating levels of soluble CD14 (?=0.72, P=0.03), CD14+CD16- monocytes (?=0.77, P=0.02), CD8+ T cell count (?=0.73, P=0.02), and CD8+PD1+ T cells (?=0.72, P=0.03). Ex-vivo experiments on banked aortic tissue demonstrated increased CD206+ macrophage infiltration among HIV-infected subjects vs. controls (30.1±7.9 vs. 14.2±7.0 macrophages/mm2 , P=0.0002) and significant tilmanocept co-localization with CD206+-staining macrophages.
Conclusions: Our findings represent a significant advance in functional imaging, utilizing a novel macrophage-specific molecular imaging strategy in humans to quantify arterial macrophage infiltration in relationship to plaque and immune indices in at-risk populations. This strategy may be useful to provide insights into immune-mediated mechanisms of atherogenesis, identify patients at risk for macrophage-mediated end organ damage, and enable future targeted delivery of immunomodulatory therapeutics.
The Thought Police: To censor and protect. Craig Bruce
