Platelet-Mimicking Therapeutic System for Noninvasive Mitigation of the Progression of Atherosclerotic Plaques.

Atherosclerotic plaque is the primary cause of cardiovascular disorders and remains a therapeutic hurdle for the early intervention of atherosclerosis. Traditional clinical strategies are often limited by surgery-related complications or unsatisfactory effects of long-term drug administration. Inspired by the plaque-binding ability of platelets, a biomimic photodynamic therapeutic system is designed to mitigate the progression of atherosclerotic plaques. This system is composed of photosensitizer-loaded upconversion nanoparticle cores entrapped in the platelet membrane. The platelet membrane coating facilitates specific targeting of the therapeutic system to macrophage-derived foam cells, the hallmark, and main component of early stage atherosclerotic plaques, which is firmly confirmed by in vivo fluorescent and single-photon emission computed tomography/computed tomography (SPECT/CT) radionuclide imaging. Importantly, in vivo phototherapy guided by SPECT/CT imaging alleviates plaque progression. Further immunofluorescence analysis reveals foam cell apoptosis and ameliorated inflammation. This biomimic system, which combines plaque-binding with radionuclide imaging guidance, is a novel, noninvasive, and potent strategy to mitigate the progression of atherosclerotic plaque.

Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism: What clinicopathologic factors affect its accuracy?

PURPOSE: Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography (MIBI-SPECT/CT) is a common technology used for primary hyperparathyroidism (PHPT) localization in clinical practice. However, the clinicopathologic factors affecting the accuracy of MIBI-SPECT/CT and the potential limitations remain unclear. METHODS: Retrospectively enrolled PHPT patients (n = 280) were analyzed from August 2017 to December 2019. RESULTS: Of 96 patients with PHPT (mean age, 54 years; 63 females), 17 had discordance between MIBI-SPECT/CT and intraoperative findings. Among the 17 patients with discordance, 58.8% had major discordance, which occurred in most patients with multigland disease (MGD). Compared with concordant patients, discordant patients exhibited increased frequencies of autoimmune thyroid disease (29.4% vs 10.1%, p = 0.035), MDG (41.2% vs 3.8%, p = 0.035), higher PTH (296 pg/mL vs 146 pg/mL; p = 0.012),and lower phosphorus levels (0.77 mmol/L vs 0.90 mmol/L; p = 0.024). MDG (odds ratio [OR], 16.95; 95% CI 2.10-142.86), parathyroid lesion size of 12 mm or less (OR, 6.93; 95% CI 1.41-34.10), and a PTH level higher than 192.5 pg/mL (OR, 12.66; 95% CI 2.17-71.43) were independently associated with discordant MIBI-SPECT/CT results. CONCLUSION: MGD was most strongly associated with discordance between MIBI-SPECT/CT and intraoperative findings followed by a PTH level higher than 192.5 pg/mL and parathyroid lesion size of 12 mm or less. Surgeons should recognize these potential limitations, which may improve the preoperative procedure by encouraging further localization imaging and promptly facilitate intraoperative troubleshooting.

Head-to-Head Comparison of 68Ga-PSMA-11 and 131I in the Follow-Up of Well-Differentiated Metastatic Thyroid Cancer: A New Potential Theragnostic Agent.

Introduction: Thyroid cancer is the main endocrine neoplasia worldwide, for which 131I therapy is the cornerstone treatment. One of the main problems of follow up in patients with this type of cancer, is the need for thyroglobulin stimulation, not to mention the poor availability of 123I or 124I, to perform studies with a higher degree of sensitivity. Prostatic Specific Membrane Antigen (PSMA) PET/CT has demonstrated to be quite useful in a diversified number of neoplasms, on behalf of its capacity of evaluating the extent of type II carboxypeptidase expression in vascular endothelium. The end point of this article is to assess whether this novel image method possesses applicability in thyroid neoplasms follow up, for diagnostic and potentially therapeutic purposes. Methods: We retrospectively evaluated well differentiated metastatic thyroid cancer patients, who underwent a post therapeutic 131I dose whole body scan (WBS) and complementary SPECT/CT, as well as 68Ga-PSMA-11 PET/CT. Results: Ten patients with differentiated thyroid cancer were included, of whom 80% were women and 20% men, mean age was 58 years old (± 11.6). Sixty-four metastatic lesions were analyzed, 67.19% had papillary histology and 32.81% were follicular type, the most affected site of metastases was bone in 57.81%, followed by lung 17.19%, lymph nodes 7.81%, postoperative thyroid bed 4.69%, brain 4.69% and others 7.81%. 68Ga PSMA-11 PET/CT detected 64/64 lesions, all of them also identified by computed tomography (CT), whereas 131I SPECT/CT detected 55/64 lesions. Discrepant lesions were localized in lung 44.4%, brain 22.2%, postoperative thyroid bed 11.1%, lymph nodes 11.1% and bone 11.1%. The degree of correspondence among observers was outstanding for both radiotracers, but close upon perfect for PSMA-11 (κ = 0.98; 95% CI, 0.80 - 0.91), as opposed to 131 I (κ = 0.86; 95% CI, 0.71 - 0.76). Conclusions: 68Ga-PSMA PET/CT showed an utterly superior capability for metastatic lesion detection when compared to 131I SPECT/CT. These findings suggest that PSMA PET/CT could possibly and precociously identify radioiodine refractoriness. PSMA uptake values not only expedite diagnosis, but also award it the ability to be used for therapeutic intents.

Functional Neurological Symptom Disorder: A Diagnostic Algorithm.

Functional neurological symptom disorder (FNSD) is a neuropsychiatric disorder characterized by the presence of neurological symptoms in the absence of any neurological abnormality that can be linked to a known pathology. Few studies have taken interest in this subject probably because of the heterogeneity of results. It is most often a diagnosis of exclusion which often means that patients undergo many tests and find themselves erring for a diagnosis with very little satisfaction of the outcomes. A reliable imagery pattern would therefore provide some relief and confirmation for both patients and clinicians. It could also facilitate acceptation of the diagnosis and reduce the societal cost associated with FNSD for the patient. The aim of this present study was to describe a clinicoradiological correspondence algorithm of FNSD using the PET scan and SPECT scan (PoSPs) and grant the clinician with a reliable tool to facilitate the diagnosis of FNSD. A systematic review according to the 2009 PRISMA criteria statement was used to guide the review. Our study included 3 of our own consenting patients who met the Diagnostic and Statistical Manual of Mental Disorders 5th edition criteria as well as 25 other patients from 7 different studies. Our results showed a hypoactivation with poor clinicoradiological correspondence and poor stability in time. This hypoactivation was mostly in the frontal lobe, which could explain some behavioral alterations. These findings oppose the ones found in organic pathologies and therefore should orient towards FNSD. In the light of these findings, we recommend the clinicians to perform two PoSPs, searching for clinicoradiological lack of correspondence and time stability using our algorithm.

Rate of elimination of radioiodine-avid lymph node metastases of differentiated thyroid carcinoma by postsurgical radioiodine ablation. A bicentric study.

SPECT/CT detects radioiodine-positive cervical lymph node metastases (LNMs) of differentiated thyroid carcinoma (DTC) at the time of postsurgical radioablation (RA). Preliminary evidence indicates that the majority of LNMs are successfully treated by RA. The aim of this study was to confirm this evidence in a bicentric setting and to evaluate whether size is a predictor for successful elimination. PATIENTS AND METHODS: Since 01/2007 and 05/2008, respectively, SPECT/spiral-CT is performed routinely in all patients with DTC at RA in two University Clinics. The outcome of iodine-positive LNMs identified by SPECT/CT until 12/2012 was analyzed by follow-up diagnostic 131I scans and serum thyreoglobulin (Tg) values. LNM volume and short-axis diameter were evaluated as prognostic factors by a receiver-operating characteristic (ROC) analysis. RESULTS: 79 patients with 97 iodine-positive LNMs were included. Surgery was carried out in 8 patients with 13 LNMs due to the presence of additional iodine-negative lesions. Of the remaining 84 LNMs, 74 (88%) were successfully treated as demonstrated by radioiodine scans at follow-up. 10 LNMs persisted. 67/70 LNMs smaller than 0.9 ml were treated successfully, whereas this was the case of only 6/14 exceeding this threshold. Using this cut-off level to predict treatment success, sensitivity, specificity, positive and negative predictive value were 92%, 73%, 96%, and 57%. Results for short-axis diameter (cut-off level < 1cm) were 90%, 69%, 94% and 56%. CONCLUSION: RA is effective in the treatment of the majority of 131I-positive LNMs identified in SPECT/CT images. In this study, 88% of iodine-positive LNM in DTC were successfully treated by radioiodine given at RA. Both LNM volume and diameter are reliable predictors of treatment success.

Cerebral blood perfusion changes in amputees with myoelectric hands after rehabilitation: a SPECT computer-aided analysis.

BACKGROUND: Rehabilitation, which is essential for amputees with myoelectric hands, can improve the quality of daily life by remodeling the neuron network. In our study, we aim to develop a cerebral blood perfusion (CBF) single-photon emission computed tomography computer-aided (SPECT-CA) detection scheme to automatically locate the brain's activated regions after rehabilitation. RESULTS: Five participants without forearms (three male, two female, mean age 51 ± 12.89 years, two missing the right side, and three missing the left side) were included in our study. In the clinical assessment, all of the participants received higher scores after training. The results of the SPM analysis indicated that CBF in the precentral gyrus, postcentral gyrus, frontal lobe, temporal lobe and cerebellum was significantly different among the five participants (P < 0.05). Moreover, SPECT-CA showed that the activated brain areas mainly included the precentral gyrus, postcentral gyrus, cerebellum and extensive cerebral cortex. CONCLUSION: Our study demonstrated that the CBF SPECT-CA method can detect the brain blood perfusion changes induced by rehabilitation with high sensitivity and accuracy. This method has great potential for locating the remodeled neuron regions of amputees with myoelectric hands after rehabilitation.

Nuclear medicine imaging of bone infections.

Osteomyelitis is a broad group of infectious diseases that involve the bone and/or bone marrow. It can arise haematogenously, via extension from a contiguous infection, or by direct inoculation during surgery or trauma. The diagnosis is not always obvious and imaging tests are frequently performed as part of the diagnostic work-up. Commonly performed radionuclide tests include technetium-99m ((99m)Tc)-diphosphonate bone scintigraphy (bone), and gallium-67 ((67)Ga) and in vitro labelled leukocyte (white blood cell; WBC) imaging. Although they are useful, each of these tests has limitations. Bone scintigraphy is sensitive but not specific, especially when underlying osseous abnormalities are present. (67)Ga accumulates in tumour, trauma, and in aseptic inflammation; furthermore, there is typically an interval of 1-3 days between radiopharmaceutical injection of and imaging. Currently, this agent is used primarily for spinal infections. Except for the spine, WBC imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. The in vitro leukocyte labelling process requires skilled personnel, is laborious, and is not always available. Complementary marrow imaging is usually required to maximise accuracy. Not surprisingly, alternative radiopharmaceuticals are continuously being investigated. Radiolabelled anti-granulocyte antibodies and antibody fragments, investigated as in vivo leukocyte labelling agents, have their own limitations and are not widely available. (111)In-biotin is useful for diagnosing spinal infections. Radiolabelled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, have shown promise as infection specific radiopharmaceuticals. 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) with or without computed tomography (CT) is very useful in musculoskeletal infection. Sensitivities of more than 95% and specificities ranging from 75-99% have been reported in acute and subacute bone and soft-tissue infection. FDG is the radionuclide test of choice for spinal infection. It is sensitive, has a high negative predictive value, and can differentiate degenerative from infectious vertebral body end-plate abnormalities. Data on the accuracy of FDG for diagnosing diabetic pedal osteomyelitis and prosthetic joint infection are inconclusive and its role for these indications remains to be determined. Other PET radiopharmaceuticals that are under investigation as infection imaging agents include gallium-68 citrate ((68)Ga) and iodine-124 fialuridine ((124)I -FIAU).

High-Sensitivity and High-Resolution SPECT/CT Systems Provide Substantial Dose Reduction Without Compromising Quantitative Precision for Assessment of Myocardial Perfusion and Function.

UNLABELLED: There is increasing concern about radiation exposure from myocardial perfusion SPECT (MPS). γ-cameras with solid-state cadmium-zinc-telluride (CZT) detectors have better count sensitivity and spatial resolution than conventional sodium iodine detectors, allowing for significant reductions in radiotracer dose or acquisition time. This study aimed to demonstrate the capability of a hybrid CZT SPECT/64-slice CT system for dose reduction and to determine the maximal reduction possible without compromising image quality or the quantification precision of clinical MPS. METHODS: The imaging data of patients with normal myocardial perfusion and 30 patients with mid-sized to large perfusion defects who had undergone stress (99m)Tc-tetrofosmin MPS were postprocessed. Low-dose (361 ± 60 MBq) and high-dose (725 ± 142 MBq) (99m)Tc-tetrofosmin scans were included, with 6-min and 4-min scanning times, respectively. List-mode SPECT data were reconstructed with CT-based attenuation correction and with full as well as 50% and 75% reductions in acquisition time to simulate the corresponding relative dose reductions. The reconstructed SPECT images were analyzed to calculate global MPS defect size and regional defect size for 3 coronary artery territories-left anterior descending, left circumflex, and right-as well as left ventricular (LV) volume and ejection fraction. RESULTS: For patients with normal MPS results, there were no differences in defect size, LV volume, or ejection fraction, regardless of whether 50% or 75% reduction was used. For patients with abnormal MPS results, at a 50% reduction there was a significant difference in global defect size but not in regional defect size in the left anterior descending, left circumflex, and right coronary artery territories, whereas at a 75% reduction the difference was statistically significant in all territories, including the difference in global defect size. Nonetheless, differences in the defect size were minimal. The LV end-diastolic and end-systolic volumes and LV ejection fraction were not significantly different, regardless of whether 50% or 75% dose reduction was used. CONCLUSION: Ultra-low-dose (<190 MBq) MPS even with short imaging times (<6 min) is feasible using a hybrid CZT SPECT/CT camera without compromising image quality or significantly altering quantification of myocardial perfusion or LV function. We demonstrated that an additional 50% reduction in the current low-dose recommendations from the American Society of Nuclear Cardiology guidelines for (99m)Tc-labeled MPS is highly feasible while retaining short imaging protocols.

Whole-remnant and maximum-voxel SPECT/CT dosimetry in 131 I-NaI treatments of differentiated thyroid cancer.

PURPOSE: To investigate the possible differences between SPECT/CT based whole-remnant and maximum-voxel dosimetry in patients receiving radio-iodine ablation treatment of differentiated thyroid cancer (DTC). METHODS: Eighteen DTC patients were administered 1.11 GBq of 131 I-NaI after near-total thyroidectomy and rhTSH stimulation. Two patients had two remnants, so in total dosimetry was performed for 20 sites. Three SPECT/CT scans were performed for each patient at 1, 2, and 3-7 days after administration. The activity, the remnant mass, and the maximum-voxel activity were determined from these images and from a recovery-coefficient curve derived from experimental phantom measurements. The cumulated activity was estimated using trapezoidal-exponential integration. Finally, the absorbed dose was calculated using S-values for unit-density spheres in whole-remnant dosimetry and S-values for voxels in maximum-voxel dosimetry. RESULTS: The mean absorbed dose obtained from whole-remnant dosimetry was 40 Gy (range 2-176 Gy) and from maximum-voxel dosimetry 34 Gy (range 2-145 Gy). For any given patient, the activity concentrations for each of the three time-points were approximately the same for the two methods. The effective half-lives varied (R = 0.865), mainly due to discrepancies in estimation of the longer effective half-lives. On average, absorbed doses obtained from whole-remnant dosimetry were 1.2 ± 0.2 (1 SD) higher than for maximum-voxel dosimetry, mainly due to differences in theS-values. The method-related differences were however small in comparison to the wide range of absorbed doses obtained in patients. CONCLUSIONS: Simple and consistent procedures for SPECT/CT based whole-volume and maximum-voxel dosimetry have been described, both based on experimentally determined recovery coefficients. Generally the results from the two approaches are consistent, although there is a small, systematic difference in the absorbed dose due to differences in the S-values, and some variability due to differences in the estimated effective half-lives, especially when the effective half-life is long. Irrespective of the method used, the patient absorbed doses obtained span over two orders of magnitude.