Photon Emission Computed Tomography Imaging Research Articles

Capturing Mercury-197m/g for Auger Electron Therapy and Cancer Theranostic with Sulfur-Containing Cyclen-Based Macrocycles.

The interest in mercury radioisotopes, 197mHg (t1/2 = 23.8 h) and 197gHg (t1/2 = 64.14 h), has recently been reignited by the dual diagnostic and therapeutic nature of their nuclear decays. These isotopes emit γ-rays suitable for single photon emission computed tomography imaging and Auger electrons which can be exploited for treating small and metastatic tumors. However, the clinical utilization of 197m/gHg radionuclides is obstructed by the lack of chelators capable of securely binding them to tumor-seeking vectors. This work aims to address this challenge by investigating a series of chemically tailored macrocyclic platforms with sulfur-containing side arms, namely, 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), and 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S). 1,4,7,10-Tetrazacyclododecane-1,4,7,10-tetracetic acid (DOTA), the widest explored chelator in nuclear medicine, and the nonfunctionalized backbone 1,4,7,10-tetrazacyclododecane (cyclen) were considered as well to shed light on the role of the sulfanyl arms in the metal coordination. To this purpose, a comprehensive experimental and theoretical study encompassing aqueous coordination chemistry investigations through potentiometry, nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, and density functional theory (DFT) calculations, as well as concentration- and temperature-dependent [197m/gHg]Hg2+ radiolabeling and in vitro stability assays in human serum was conducted. The obtained results reveal that the investigated chelators rapidly complex Hg2+ in aqueous media, forming extremely thermodynamically stable 1:1 metal-to-ligand complexes with superior stabilities compared to those of DOTA or cyclen. These complexes exhibited 6- to 8-fold coordination environments, with donors statically bound to the metal center, as evidenced by the presence of 1H-199Hg spin-spin coupling via NMR. A similar octacoordinated environment was also found for DOTA in both solution and solid state, but in this case, multiple slowly exchanging conformers were detected at ambient temperature. The sulfur-rich ligands quantitatively incorporate cyclotron-produced [197m/gHg]Hg2+ under relatively mild reaction conditions (pH = 7 and T = 50 °C), with the resulting radioactive complexes exhibiting decent stability in human serum (up to 75% after 24 h). By developing viable chelators and understanding the impact of structural modifications, our research addresses the scarcity of suitable chelating agents for 197m/gHg, offering promise for its future in vivo application as a theranostic Auger-emitter radiometal.

Radionuclide labeled nanocarrier for imaging guided combined radionuclide, sonodynamic, and photothermal therapy of pancreatic tumours

Radionuclide therapy (RNT) is an effective method for the clinical precise treatment of cancer. However, the uneven dose distribution and rapid metabolism of nuclides limit the effective killing of tumors. To overcome the limitations of radionuclide therapeutic approaches, combining different therapeutic strategies to treat cancer has manifested great promise in basic and clinical research. Here, a new combination therapy strategy was developed to combine radionuclide therapy, sonodynamic therapy and photothermal therapy (RNT-SDT-PTT) under radionuclide imaging guided achieve highly effective combination therapy. We prepared a polydopamine-modified Au nanostar (AN), then loaded with the acoustic sensitizer protoporphyrin (IX) and labeled with diagnostic (99mTc) or therapeutic (131I) radionuclides (131I/99mTc-AN@D/IX) for the precise diagnosis and treatment of pancreatic cancer. After intratumor administration, single photon emission computed tomography imaging showed that the nanocarriers were mostly retained in the tumor compared to free radionuclide. As well as using near-infrared light to trigger PTT and ultrasound with high penetration depth to activate IX to generate reactive oxygen species achieved SDT of tumor. The ultimate significantly improved the inhibitory effects by the RNT-SDT-PTT combined therapy for pancreatic cancer. Therefore, this study proposes an effective radionuclide combination therapy regimen consisting of three widely used treatments, offering promising prospects for the future of oncology.

Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease.

Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [123 I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density. To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD. We assessed clinical features, the peripheral immune profile, and striatal [123 I]FP-CIT DAT binding levels of 211 patients with PD (primary-cohort). Covariate-controlled associations between the immune response and striatal DAT levels were assessed using linear regression analyses. For replication purposes, we also studied a separate cohort of 344 de novo patients with PD enrolled in the Parkinson's Progression Markers Initiative (PPMI-cohort). A higher NLR was significantly associated with lower DAT levels in the caudate (primary-cohort: β=-0.01, p < 0.001; PPMI-cohort: β=-0.05, p=0.05) and the putamen (primary-cohort: β=-0.05, p=0.02; PPMI-cohort: β=-0.06, p=0.02). Intriguingly, a lower lymphocyte count was significantly associated with lower DAT levels in both the caudate (primary-cohort: β=+0.09, p < 0.05; PPMI-cohort: β=+0.11, p=0.02) and the putamen (primary-cohort: β=+0.09, p < 0.05, PPMI-cohort: β=+0.14, p=0.01), but an association with the neutrophil count was not consistently observed (caudate; primary-cohort: β=-0.05, p=0.02; PPMI-cohort: β=0, p=0.94; putamen; primary-cohort: β=-0.04, p= 0.08; PPMI-cohort: β=-0.01, p= 0.73). Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Characterization and Efficacy of a Nanomedical Radiopharmaceutical for Cancer Treatment.

Although much progress has been made over the last decades, there is still a significant clinical need for novel therapies to manage cancer. Typical problems are that solid tumors are frequently inaccessible, aggressive, and metastatic. To contribute to solving some of these issues, we have developed a novel radioisotope-labeled 27 nm nanoparticle, 177Lu-SN201, to selectively target solid tumors via the enhanced permeability and retention effect, allowing irradiation intratumorally. We show that 177Lu-SN201 has robust stealth properties in vitro and anti-tumor efficacy in mouse mammary gland and colon carcinoma models. The possible clinical application is also addressed with single photon emission computed tomography imaging, which confirms uptake in the tumor, with an average activity of 19.4% injected dose per gram (ID/g). The properties of 177Lu-SN201 make it a promising new agent for radionuclide therapy with the potential to target several solid tumor types.

Agreement between Thai Cardiovascular Risk Scores and Myocardial Perfusion Imaging: Exploring Associations and Clinical Implications.

This study aimed to assess the agreement between the Thai cardiovascular (CV) risk score or pretest probability (PTP), and myocardial perfusion imaging (MPI), and to explore the association between abnormal MPI results and higher Thai CV risk scores or PTP risk. The study was conducted between March 2017 and December 2021, and included 128 patients. Myocardial perfusion gated single photon emission computed tomography imaging was performed on all patients, and agreement between the Thai CV risk score, PTP, and MPI was measured using weighted Cohen's kappa statistic. Logistic regression was used to calculate odds ratios (OR) and explore the association. Fair agreement was observed between MPI and the Thai CV risk score (κ =0.269, P = 0.010), including patients with clinical chest pain (κ =0.367, P < 0.001). Subgroup analysis of patients with intermediate PTP revealed moderate agreement between MPI and the Thai CV risk score (κ =0.428, P = 0.002). Patients with intermediate (OR = 3.25, P = 0.010) or high (OR = 4.78, P = 0.001) Thai CV risk scores had significantly higher odds of having intermediate or high MPI results compared to those with low Thai CV risk scores. This study highlights the agreement between MPI and the Thai CV risk score and PTP. Higher Thai CV risk scores are associated with increased odds of abnormal MPI results. These findings provide valuable insights for clinical decision-making and patient management.

Modeling families of particle distributions with conditional GAN for Monte Carlo SPECT simulations

Objective. We propose a method to model families of distributions of particles exiting a phantom with a conditional generative adversarial network (condGAN) during Monte Carlo simulation of single photon emission computed tomography imaging devices. Approach. The proposed condGAN is trained on a low statistics dataset containing the energy, the time, the position and the direction of exiting particles. In addition, it also contains a vector of conditions composed of four dimensions: the initial energy and the position of emitted particles within the phantom (a total of 12 dimensions). The information related to the gammas absorbed within the phantom is also added in the dataset. At the end of the training process, one component of the condGAN, the generator (G), is obtained. Main results. Particles with specific energies and positions of emission within the phantom can then be generated with G to replace the tracking of particle within the phantom, allowing reduced computation time compared to conventional Monte Carlo simulation. Significance. The condGAN generator is trained only once for a given phantom but can generate particles from various activity source distributions.

Optimum Combination of Radiopharmaceuticals‐Based Targeting‐Triggering‐Therapy Effect and PD‐L1 Blockade Immunotherapy

AbstractThe therapeutic alliance of 177Lu radioligand therapy and immune checkpoint blockade (ICB) has gained increasing attention. This study aims to investigate the immunomodulatory effect (targeting‐triggering‐therapy) of 177Lu‐DOTA‐EB‐cRGDfK (177Lu‐DER) and to optimize the therapeutic efficacy by combining targeted radionuclide therapy (TRT) and ICB. Flow cytometry, immunofluorescence analysis, and RT‐qPCR are conducted to confirm the change of PD‐L1 expression. Tumor uptakes of 177Lu‐DER in CT26 and MC38 colorectal tumor models are verified through single photon emission computed tomography imaging. Further, the radionuclide dose and the treatment schedule to optimize the therapeutic scheme are carefully titrated and the mechanism of the synergy between TRT and ICB is explored. The results demonstrate that PD‐L1 expression is upregulated after irradiation of 177Lu. The combination of 9.25 MBq 177Lu‐DER TRT with 200 µg αPD‐L1 immunotherapy significantly inhibits tumor growth and protects against tumor recurrence. It is also found that 4‐h interval is an effective time window between radioligand administration and ICB therapy. In conclusion, a promising scheme for tumor immunotherapy is realized based on the sequential administration of integrin αvβ3‐targeted radioligand and PD‐L1 immune checkpoint blocker, emphasizing the potential of combining radiotheranostics with ICB for precision cancer therapy.

Functionalization of Radiolabeled Antibodies to Enhance Peripheral Clearance for High Contrast Brain Imaging.

Small molecule imaging agents such as [11C]PiB, which bind to the core of insoluble amyloid-β (Aβ) fibrils, are useful tools in Alzheimer's disease (AD) research, diagnostics, and drug development. However, the [11C]PiB PET signal saturates early in the disease progression and does not detect soluble or diffuse Aβ pathology which are believed to play important roles in the disease progression. Antibodies, modified into a bispecific format to enter the brain via receptor-mediated transcytosis, could be a suitable alternative because of their diversity and high specificity for their target. However, the circulation time of these antibodies is long, resulting in an extended exposure to radiation and low imaging contrast. Here, we explore two alternative strategies to enhance imaging contrast by increasing clearance of the antibody ligand from blood. The bispecific Aβ targeting antibody RmAb158-scFv8D3 and the monospecific RmAb158 were radiolabeled and functionalized with either α-d-mannopyranosylphenyl isothiocyanate (mannose) or with trans-cyclooctene (TCO). While mannose can directly mediate antibody clearance via the liver, TCO-modified antibody clearance was induced by injection of a tetrazine-functionalized, liver-targeting clearing agent (CA). In vivo experiments in wild type and AD transgenic mice demonstrated the ability of both strategies to drastically shorten the circulation time of RmAb158, while they had limited effect on the bispecific variant RmAb158-8D3. Furthermore, single photon emission computed tomography imaging with TCO-[125I]I-RmAb158 in AD mice showed higher contrast 1 day after injection of the tetrazine-functionalized CA. In conclusion, strategies to enhance the clearance of antibody-based imaging ligands could allow imaging at earlier time points and thereby open the possibility to combine antibodies with short-lived radionuclides such as fluorine-18.

Peptide Receptor Radionuclide Therapy.

The concept of using a targeting molecule labeled with a diagnostic radionuclide for using positron emission tomography or single photon emission computed tomography imaging with the potential to demonstrate that tumoricidal radiation can be delivered to tumoral sites by administration of the same or a similar targeting molecule labeled with a therapeutic radionuclide termed "theranostics." Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs (SSAs) is a well-established second/third-line theranostic treatment for somatostatin receptor-positive well-differentiated (neuro-)endocrine neoplasms (NENs). PRRT with 177Lu-DOTATATE was approved by the regulatory authorities in 2017 and 2018 for selected patients with low-grade well-differentiated gastroenteropancreatic (GEP) NENs. It improves progression-free survival as well as quality of life of GEP NEN patients. Favorable symptomatic and biochemical responses using PRRT with 177Lu-DOTATATE have also been reported in patients with functioning metastatic GEP NENs like metastatic insulinomas, Verner Morrison syndromes (VIPomas), glucagonomas, and gastrinomas and patients with carcinoid syndrome. This therapy might also become a valuable therapeutic option for inoperable low-grade bronchopulmonary NENs, inoperable or progressive pheochromocytomas and paragangliomas, and medullary thyroid carcinomas. First-line PRRT with 177Lu-DOTATATE and combinations of this therapy with cytotoxic drugs are currently under investigation. New radiolabeled somatostatin receptor ligands include SSAs coupled with alpha radiation emitting radionuclides and somatostatin receptor antagonists coupled with radionuclides.

Accuracy and Reproducibility of Myocardial Blood Flow Quantification by Single Photon Emission Computed Tomography Imaging in Patients With Known or Suspected Coronary Artery Disease.

Single photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99mTc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique. Accuracy was assessed in 34 participants who underwent dynamic 99mTc-sestamibi SPECT and 13N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99mTc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model' and MFR was derived as the stress/rest MBF ratio. SPECT global MBF with splines showed good correlation with 13N-ammonia positron emission tomography (r=0.81, P<0.001) and MFR estimates (r=0.74, P<0.001). Correlations were substantially weaker for standard reconstruction without splines (r=0.61, P<0.001 and r=0.34, P=0.07, for MBF and MFR, respectively). Reproducibility of global MBF estimates with splines in paired SPECT scans was good (r=0.77, P<0.001), while ordered subset expectation maximization without splines led to decreased MBF (r=0.68, P<0.001) and MFR correlations (r=0.33, P=0.3). There were no significant differences in MBF or MFR between the 2 reproducibility scans independently of the reconstruction algorithm (P>0.05 for all). MBF and MFR quantification using 99mTc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation.

The ‘ramp filter’ artifact in filtered back projection is due to attenuation not ramp filtering

Artifactually decreased counts in regions of the left ventricle adjacent to intense splanchnic activity have been described in single photon emission computed tomography imaging and attributed to the side lobes of ramp filtering, a crucial step in filtered back projection. However, filtered back projection is based on a mathematical proof that makes no assumptions about the distribution of activity implying there is another cause for this artifact. Computer simulations of a left ventricle with varying intensity, proximity and size of adjacent splanchnic activity was created with and without attenuation. Both filtered back projection and an iterative expectation maximization algorithm were performed. Volume weighted bullseyes were generated then the ratio of average activity in regions in the anterior and inferior walls of the bullseye were calculated. In the absence of attenuation, there was no effect on uptake despite intense adjacent splanchnic activity. The effect of attenuation alone was mild but was greatly amplified by adjacent splanchnic uptake. This effect varied with the intensity, proximity and size of adjacent activity. Moving the attenuation to the apex of the left ventricle produced a paradoxical increase in counts to the inferior wall. The effect on iterative reconstruction was less pronounced than with filtered back projection and the paradoxical increase with attenuation at the apex did not occur. The ramp filter artifact in single photon emission computed tomography reconstruction is due to attenuation, not ramp filtering per se. Adjacent splanchnic activity can result in either an increase or decrease in counts. These effects are less pronounced and more consistent with iterative reconstruction.

Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives.

COVID-19 pandemic has heightened the interest toward diagnosis and treatment of infectious diseases. Nuclear medicine with its powerful scintigraphic, single photon emission computer tomography (SPECT) and positron emission tomography (PET) imaging modalities has always played an important role in diagnosis of infections and distinguishing them from the sterile inflammation. In addition to the clinically available radiopharmaceuticals there has been a decades-long effort to develop more specific imaging agents with some examples being radiolabeled antibiotics and antimicrobial peptides for bacterial imaging, radiolabeled anti-fungals for fungal infections imaging, radiolabeled pathogen-specific antibodies and molecular engineered constructs. In this opinion piece, we would like to discuss some examples of the work published in the last decade on developing nuclear imaging agents for bacterial, fungal, and viral infections in order to generate more interest among nuclear medicine community toward conducting clinical trials of these novel probes, as well as toward developing novel radiotracers for imaging infections.

Sustained Activity of Stimuli-Responsive Curcumin and Acemannan Based Hydrogel Patches in Wound Healing.

Natural plant extract, namely acemannan (Ac) and curcumin (Cur), coencapsulated pluronic micelles, showing thermoresponsive properties, were designed for efficient and safe in vivo wound healing applications. Ac and Cur, widely used antimicrobials, find limited applications because of their low stability, short biological half-life, poor solubility, and low bioavailability. Herein, we report the extraction of Ac from aloe vera and coencapsulation of it with Cur in pluronic micelles to take advantage of the combined effects of both components. Both Ac and Cur preserved their bioactive functionality upon encapsulation. Single photon emission computed tomography imaging confirmed that NPAcC2 hydrogel masked the whole wound by forming a layer. Cur and Ac synergistically resulted in rapid wound closure on the seventh day, and full-grown hair was observed on the 10th day. Individually they both take more than 20 days for wound closure. The increase in the concentration of curcumin increases the healing properties of the material. For days 1, 6, and 10 of the wound dressing experiment, the percentages of wound closure of the mice were the highest for NPAcC2 (i.e., 100%) compared to the untreated control (25%) while maintaining the integrity of the skin. These natural product-based hydrogels have limited side effects vs those caused by commercial drugs in wound healing.

TECHNETIUM-99M MIBI GATED MYOCARDIAL PERFUSION SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY IMAGING – VALIDATION OF STRESS ONLY PROTOCOL

Objective: To validate ‘stress only’ protocol against ‘rest stress protocol in normal and essentially normal cases undergoing Tc99m MIBI gated myocardial perfusion Single Photon Emission Computed Tomography imaging.&#x0D; Study Design: A retrospective observational study.&#x0D; Place and Duration of Study: Department of Nuclear Cardiology, Armed Forces Institute of Cardiology/National Institute of Heart Disease, Rawalpindi, Pakistan, from Jul to Sep 2019.&#x0D; Methodology: 136 cases were included. Patients underwent Tc-99m gated Single Photon Emission Computed Tomography MPI using a single day, rest/stress protocol. The rest study was performed first with 8-10 mCi Tc-99m MIBI followed by stress study, 3 hours later with 3 times the rest dose. The most common stress technique was pharmacological stress and bicycle ergometer exercise with 0.14 mg/kg/min adenosine infusion. Few patients underwent physical stress using Bruce protocol, achieving a minimum of 85% of the target heart rate. Mages–stress followed by rest–were evaluated by two experienced nuclear cardiologists (blinded to the MPI reports) and interpreted as ‘normal’ or ‘essentially normal’.&#x0D; Results: Evaluation of stress-only and rest-stress Single Photon Emission Computed Tomography myocardial images yielded a concordance rate of 84.56% with Cohen’s kappa coefficient of 0.69.&#x0D; Conclusion: Substantial agreement and good concordance were found in normal and essentially normal ‘stress only’ and ‘rest stress protocols.

An image processing tool for the detection of anthracycline-induced cardiotoxicity by evaluating the myocardial metabolic activity in [18F]FDG PET/CT

PurposeChemotherapy-induced cardiotoxicity is one of the main complications during and after cancer treatment. While echocardiography is the most used technique in clinical practice to evaluate left ventricular (LV) dysfunction, a multimodal approach is preferred for the early detection of anthracycline-induced cardiotoxicity. In this paper, an image processing tool allowing the qualitative and quantitative analysis of myocardial metabolic activity by [18F]fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) images, acquired routinely during and after cancer treatment, is presented.MethodsThe methodology is based on cardiac single photon emission computed tomography image processing protocols used in clinical practice. LV polar maps are created, and quantitative regional values are calculated. The tool was validated in a study group of 24 patients with Hodgkin or non-Hodgkin lymphoma (HL and NHL, respectively) treated with anthracyclines. Staging, interim and end-of-treatment [18F]FDG PET/CT images were acquired and the presented tool was used to extract the quantitative metrics of LV metabolic activity.ResultsResults show an overall increase of metabolic activity in the interim PET image acquired while on treatment compared to staging PET, which then decreased in the end-of-treatment scan. Positive correlation coefficients between staging and interim scans, and negative correlation coefficients between interim and end-of-treatment scans also support this finding. Metabolic changes occur predominantly in the septal region.ConclusionThe proposed methodology and presented software solution provides the capability to assess quantitatively myocardial metabolism acquired by routine [18F]FDG PET/CT scanning during cancer treatment for evaluating anthracycline-induced cardiotoxicity. The [18F]FDG PET/CT septal-lateral uptake ratio is proposed as a new quantitative measure of myocardial metabolism.

Cardiac Scintigraphy and Screening for Transthyretin Cardiac Amyloidosis: Caveat Emptor.

Cardiac Scintigraphy and Screening for Transthyretin Cardiac Amyloidosis: Caveat Emptor.

Applied machine learning for liver surgery

Abstract Background and objectives: Both hepatic functional reserve and the underlying histology are important determinants in the preoperative risk evaluation before major hepatectomies. In this project we developed a new approach that implements cutting-edge research in machine learning and nevertheless is cheap and easily applicable in a routine clinical setting is needed. Methods: After splitting the study population into a training and test set we trained a convolutional neural network to predict the liver function as determined by hepatobiliary mebrofenin scintigraphy and single photon emission computer tomography (SPECT) imaging. Results: We developed a workflow for predicting liver function from routine CT imaging data using convolutional neural networks. We also evaluated in how far transfer learning and data augmentation can help to solve remaining manual data pre-processing steps and implemented the developed workflow in a clinical routine setting. Conclusion: We propose a robust semiautomatic end-to-end classification workflow for abdominal CT scans for the prediction of liver function based on a deep convolutional neural network model that shows reliable and accurate results even with limited computational resources.

Synthesis and evaluation of technetium-99m labelled 1-(2-methoxyphenyl)piperazine derivative for single photon emission computed tomography imaging for targeting 5-HT1A

Quantitative changes in expression level of 5HT1A are somewhere related to common neurological disorders such as anxiety, major depression and schizophrenia. We have designed EDTA conjugated SPECT imaging probe for localization of 5HT1A receptor in brain. For designing SPECT probe we have employed the concept of bivalent approach and a homodimeric system with desirable pharmacokinetics of 5HT1A imaging. 99mTc-EDHT was also evaluated for its stability through serum stability assay and glutathione challenge experiment. Biodistribution study showed the highest accumulation of radioactivity in kidney which depicted the renal mode of excretion from the body. However in brain the uptake of 1.21% ID per gram was observed in initial 5 min of drug administration. On blocking the receptor this percent get decreased to 0.97% ID per gram. The regional distribution in brain was also performed which showed the accumulation of drug in cerebellum, cortex and hippocampus part, which are already known for 5HT1A expression. Dynamic study in rabbit is also in support of results derived from biodistribution and blood kinetics experiment. These finding suggest that 99mTc-EDHT holds promising place for further optimization before nuclear medicine applications in different animal species.

The slope of cerebral oxyhemoglobin oscillation is associated with vascular reserve capacity in large artery steno-occlusion

Inadequate cerebral perfusion is a risk factor for cerebral ischemia in patients with large artery steno-occlusion. We investigated whether prefrontal oxyhemoglobin oscillation (ΔHbO2, 0.6–2 Hz) was associated with decreased vascular reserve in patients with steno-occlusion in the large anterior circulation arteries. Thirty-six patients with steno-occlusion in the anterior circulation arteries (anterior cerebral artery, middle cerebral artery, and internal carotid artery) were included and compared to thirty-six control subjects. Patients were categorized into two groups (deteriorated vascular reserve vs. preserved vascular reserve) based on the results of Diamox single- photon emission computed tomography imaging. HbO2 data were collected using functional near-infrared spectroscopy. The slope of ΔHbO2 and the ipsilateral/contralateral slope ratio of ΔHbO2 were analyzed. Among the included patients (n = 36), 25 (69.4%) had deteriorated vascular reserve. Patients with deteriorated vascular reserve had a significantly higher average slope of ΔHbO2 on the ipsilateral side (5.01 ± 2.14) and a higher ipsilateral/contralateral ratio (1.44 ± 0.62) compared to those with preserved vascular reserve (3.17 ± 1.36, P = 0.014; 0.93 ± 0.33, P = 0.016, respectively) or the controls (3.82 ± 1.69, P = 0.019; 0.94 ± 0.29, P = 0.001). The ipsilateral/contralateral ΔHbO2 ratio could be used as a surrogate for vascular reserve in patients with severe steno-occlusion in the anterior circulation arteries.

Improvement of signal and noise performance using single image super-resolution based on deep learning in single photon-emission computed tomography imaging system

Because single-photon emission computed tomography (SPECT) is one of the widely used nuclear medicine imaging systems, it is extremely important to acquire high-quality images for diagnosis. In this study, we designed a super-resolution (SR) technique using dense block-based deep convolutional neural network (CNN) and evaluated the algorithm on real SPECT phantom images. To acquire the phantom images, a real SPECT system using a99mTc source and two physical phantoms was used. To confirm the image quality, the noise properties and visual quality metric evaluation parameters were calculated. The results demonstrate that our proposed method delivers a more valid SR improvement by using dense block-based deep CNNs as compared to conventional reconstruction techniques. In particular, when the proposed method was used, the quantitative performance was improved from 1.2 to 5.0 times compared to the result of using the conventional iterative reconstruction. Here, we confirmed the effects on the image quality of the resulting SR image, and our proposed technique was shown to be effective for nuclear medicine imaging.