Investigation of nanomaterial disposition and fate in the body is critical before such material can be translated into clinical application. Herein a new macrocyclic ligand–64Cu2+ complex was synthesized and used to label dextran-coated silicon quantum dots (QD), with an average hydrodynamic diameter of 15.1 ± 7.6 nm. The chelate showed exceptional stability, demonstrated by no loss radiolabel under a ligand competition reaction with EDTA. The QDs’ biodistribution in mice was quantitatively evaluated by in vivo positron emission tomography (PET) imaging and ex vivo gamma counting. Results showed that they were excreted via renal filtration shortly postinjection and also accumulated in the liver.
In a number of literature reports iron oxide nanoparticles have been investigated for use in imaging atherosclerotic plaques and found to accumulate in plaques via uptake by macrophages, which are critical in the process of atheroma initiation, propagation, and rupture. However, the uptake of these agents is nonspecific, thus the labeling efficiency for plaques in vivo is not ideal. We have developed targeted agents to improve the efficiency for labeling macrophage-laden plaques. These probes are based on iron oxide nanoparticles coated with dextran sulfate, a ligand of macrophage scavenger receptor type A (SR-A). We have sulfated dextran-coated iron oxide nanoparticles (DIO) with sulfur trioxide, thereby targeting our nanoparticle imaging agents to SR-A. The sulfated DIO (SDIO) remained mono-dispersed and had an average hydrodynamic diameter of 62 nm, an r1 relaxivity of 18.1 mM−1s−1, and an r2 relaxivity of 95.8 mM−1s−1 (37 °C, 1.4 T). Cell studies confirmed that these nanoparticles were nontoxic and specifically targeted to macrophages. In vivo MRI after intravenous injection of the contrast agent into an atherosclerotic mouse injury model showed substantial signal loss on the injured carotid at 4 and 24 hours post-injection of SDIO. No discernable signal decrease was seen at the control carotid and only mild signal loss was observed for the injured carotid post-injection of non-sulfated DIO, indicating preferential uptake of the SDIO particles at the site of atherosclerotic plaque. These results indicate that SDIO can facilitate MRI detection and diagnosis of vulnerable plaques in atherosclerosis.
Objectives/Hypothesis: To assess the accuracy and utility of positron emission tomography/computed tomography (PET/CT) compared with magnetic resonance imaging (MRI) for detecting head and neck cancer (HNC) recurrence after microvascular reconstructive surgery.Study Design: Retrospective cohort study. Methods: Analysis of HNC patients who underwent microvascular reconstruction at a single, tertiary academic center following ablative surgery from 1998 to 2015. Forty-six patients aged 61.4 AE 15.8 years with both PET/CT and MRI examinations were identified. Two radiologists were blinded and interpreted each imaging study. Recurrence certainty scores were determined via continuous (0-100) and Likert ("Likely" to "Unlikely") scales, with larger values indicating a higher likelihood of recurrence. Pathologic confirmation of recurrence was confirmed in 23 patients (50%).Results: Among those with primary site recurrences, mean recurrence certainty was significantly higher with PET/CT versus MRI on the continuous scale (63.9 vs. 44.4, P = .006). A receiver operating characteristic analysis for predicting primary site recurrence demonstrated a significantly larger area under the curve of 0.79 for PET/CT compared to 0.64 for MRI (P = .044). Categorization of "Likely" primary site recurrence on PET/CT, versus MRI, had higher sensitivity (0.63 vs. 0.40), but lower specificity (0.90 vs. 1.0). MRI demonstrated higher sensitivity (1.0 vs. 0.78) at detecting regional site recurrences.Conclusion: PET/CT demonstrates greater sensitivity than MRI as a surveillance tool for primary site recurrence following microvascular reconstruction where clinical evaluation is hindered by anatomical distortion. Therefore, PET/CT should be pursued as first-line imaging, with MRI utilized for confirmation of positive imaging findings at the primary site.
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