Inspired by novel radiopharmaceuticals:Rush hour of nuclear medicine

Nuclear medicine plays an irreplaceable role in the diagnosis and treatment of tumors.Radiopharmaceuticals are important components of nuclear medicine.Among the radiopharmaceuticals approved by the Food and Drug Administration(FDA),radio-tracers targeting prostate-specific membrane antigen(PSMA)and somatostatin receptor(SSTR)have held essential positions in the diagnosis and treatment of prostate cancers and neuroendocrine neoplasms,respectively.In recent years,FDA-approved serials of immune-therapy and targeted therapy drugs targeting programmed death 1(PD-1)/programmed death ligand 1(PD-L1),human epidermal growth factor receptor 2(HER2),and nectin cell adhesion molecule 4(Nectin 4).How to screen patients suitable for these treatments and monitor the therapy?Nuclear medicine with specific radiopharmaceuticals can visualize the expression level of those targets in systemic lesions and evaluate the efficacy of treatment.In addition to radiopharmaceuticals,imaging equipment is also a key step for nuclear medicine.Advanced equipment including total-body positron emission tomography/computed tomography(PET/CT)and positron emission tomography/magnetic resonance imaging(PET/MRI)has been developed,which contribute to the diagnosis and treatment of tumors,as well as the development of new radiopharmaceuticals.Here,we conclude most recently advances of radiopharmaceuticals in nuclear medicine,and they substantially increase the“arsenal”of clinicians for tumor therapy.

Rheumatoid arthritis: Nuclear medicine state-of-the-art imaging

Rheumatoid arthritis(RA)is an autoimmune disease,which is associated with systemic and chronic inflammation of the joints,resulting in synovitis and pannus formation.For several decades,the assessment of RA has been limited to conventional radiography,assisting in the diagnosis and monitoring of disease.Nevertheless,conventional radiography has poor sensitivity in the detection of the inflammatory process that happens in the initial stages of RA.In the past years,new drugs that significantly decrease the progression of RA have allowed a more efficient treatment.Nuclear Medicine provides functional assessment of physiological processes and therefore has significant potential for timely diagnosis and adequate follow-up of RA.Several single photon emission computed tomography(SPECT)and positron emission tomography(PET)radiopharmaceuti-cals have been developed and applied in this field.The use of hybrid imaging,which permits computed tomography(CT)and nuclear medicine data to be acquired and fused,has increased even more the diagnostic accuracy of Nuclear Medicine by providing anatomical localization in SPECT/CT and PET/CT studies.More recently,fusion of PET with magnetic resonance imaging(PET/MRI)was introduced in some centers and demonstrated great potential.In this article,we will review studies that have been published using Nuclear Medicine for RA and examine key topics in the area.

Recommendations on Strengthening the Development of Nuclear Medicine in China

This paper outlines briefly the role of nuclear medicine in life sciences and health care. Molecular imaging by using isotopic tracers can noninvasively visualize the chemistry or hidden process in the cells and tissues inside the body, obtaining "functional" images to provide early information of any disease and revealing the secrets of life. The vitality of nuclear medicine is its ability to translate bench into new clinical application that can benefits the patients. Although nuclear medicine community in China has made significant achievement with a great effort since 1950s, there are many obstacles to future development. Recommended measures are proposed here in an attempt to solve our existing problems.

Assessment of Patient and Staff Annual Effective Doses at a Nuclear Medicine Department during Bone Scans

The current research aims to assess the staff and patients’ effective doses during Nuclear medicine (NM) bone scans procedures. The administered activity was utilized to quantify the patients’ effective doses, while personnel’s effective doses were quantified using thermoluminescent detectors (TLD-100). The average administered activity was 650 (440 to 1440) MBq procedures using SPECT gamma camera system. The average annual staff effective dose (mSv) was estimated to be 2.3 (0.1 to 4.9). The typical patient’s effective dose was 4.9 (3.6 to 6.0) mSv per procedure. Staff exposure within the yearly effective dose limits. Patients’ exposure optimization is required based on patient weight. Estimating staff eye lens doses is suggested to confirm that the yearly effective radiation doses are within the safety range.

Establishment of Dose Reference Levels for Nuclear Medicine in Sudan

In this study, a national survey for establishment of Nuclear Medicine (NM) Dose Reference Levels (DRLs) for adult patients was carried out. The Administrated Activity (AAs) (MBq) was collected from six nuclear medicine departments. Factors influencing the image quality were also observed. The established Sudan National DRLs represent the AA value corresponding to 75th percentile of the AA frequency distribution. Generally, Sudan National DRLs and average AAs are comparable with the papers published in the international literature. All Sudanese DRLs values were found within the international range. While it is noted that the Sudanese DRLs is higher than the values of ARSA except for the MIBI pharmaceuticals that used in both parathyroid and myocardial perfusion scan and for 99mTcDTPA that used for Dynamic Renal scan study the DRLs values were decreased. In compared with UNSCEAR 2008 data, the average dose (MBq) for Sudanese we note that the bone scan falls within the average values while it’s lower in all other scans except for parathyroid scan in which the AAAs increase more than twice. When compared to BSS 1996, it showed variation in increased and decreased AAAs. There may be potential for reducing the higher values of AAs, in co-operation with Nuclear Medicine staff.

A Pretargeting Strategy Enabled by Bioorthogonal Reactions Towards Advanced Nuclear Medicines: Application and Perspective

Pretargeting is an innovative and promising approach in nuclear medicine for targeted-imaging/therapy through the following bioorthogonal reactions.It requires two reactive participants,one of which is a targeting vector and the other is a small radiolabeled probe capable of specifically coupling through bioorthogonal reactions with the targeting vector accumulated in the disease site.Compared to the conventional direct targeting approach,such a two-step scheme conceptually can achieve a higher imaging contrast and an improved therapeutic effect owing to the suppressed non-specific targeting.In this review,we will first give a brief introduction on pretargeting systems and the history of bioorthogonal reactions,and then focus on some important works about radionuclide delivering through the bioorthogonal reaction based pretargeting strategy.Finally,we will discuss the steps forward in respect to the future clinical translation and truly hope that this methodology would continue to make contributions to nuclear medicines.

Contribution of Metabolic Imaging in the Exploration of Cognitive Disorders Related to COVID-19

On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was favored to assess lung lesions. In addition, many cases of post-COVID-19 cognitive disorders have been reported. As the curve dips and services restart correctly, other imaging techniques have been used to better explore the disease. The objective of this presentation is to illustrate the contribution of metabolic imaging in the exploration of post COVID-19 cognitive disorders and to discuss the pathophysiological mechanisms. Hypometabolism brain lesions are objective signs of functional impairment whose pathophysiological mechanism is not yet fully understood. Metabolic imaging with PET-SCAN is a suitable tool for exploring these disorders, both for the severity and extent of the lesions and for the topography of the brain damage.

Effect of teach-back health education combined with structured psychological nursing on adverse emotion and patient cooperation during 99mTc-3PRGD2.SPECT/CT

BACKGROUND 99mTc-3PRGD2.SPECT/CT is a commonly used examination method in nuclear medicine.However,patients receiving 99mTc-3PRGD2.SPECT/CT have insufficient knowledge of this method and worry about the examination results.AIM To investigate the effect of teach-back health education combined with structured psychological nursing on adverse emotion and cooperation in patients undergoing 99mTc-3PRGD2.SPECT/CT examination.METHODS Ninety patients undergoing 99mTc-3PRGD2.SPECT/CT examinations were divided into a study group and a control group using a simple random number table,and 45 cases were allocated to each group.Routine nursing was provided to the control group,and teach-back health education combined with structured psychological nursing was provided to the study group on the basis of the control group.Heart rate,diastolic blood pressure,systolic blood pressure,self-rating depression scale(SDS),and self-rating anxiety scale(SAS)were assessed before and after the intervention,and examination cooperation and intervention satisfaction were assessed in the two groups before,during,and after the examination.RESULTS Before the examination,heart rate,diastolic blood pressure,and systolic blood pressure in the study group were not significantly different from the values of the control group(P>0.05).The results of the study group before and after the examination were lower than those in the control group(P<0.05).Before the intervention,SDS and SAS scores in the study group were not significantly different from those in the control group(P>0.05).After the intervention,SDS and SAS scores in the study group were lower than those in the control group(P<0.05).The degree of cooperation was higher in the study group than in the control group(P<0.05).The satisfaction rate with the intervention was higher in the study group than in the control group(P<0.05).CONCLUSION Teach-back health education combined with structured psychological nursing can help maintain the stability of blood pressure and heart rate,relieve negative emotions,and improve the satisfaction and cooperation of patients undergoing 99mTc-3PRGD2.SPECT/CT examinations.

Somatostatin receptor scintigraphy in the follow up of neuroendocrine neoplasms of appendix

BACKGROUND Neuroendocrine tumors of appendix(ANETs)known as carcinoids,are rare endocrine neoplasms originated from enterochromaffin cells of gastrointestinal tract.ANETs are the third most frequent(16.7%)gastrointestinal neuroendocrine tumors,with the incidence of 0.08-0.2 cases/100000 during one year.Incidental ANETs occur in 0.2%-0.7%of emergency surgical resections because of suspected appendicitis which is usually the first manifestation of ANET.Although there are a lot of papers about application of somatostatin receptor scintigraphy in gastrointestinal neuroendocrine tumors,there are very rare sporadic cases described about ANETs particularly.AIM To establish the role of somatostatin receptor scintigraphy(SRS)in the management of patients with neuroendocrine tumors of appendix(ANET).METHODS The total of 35 patients was investigated,23 females and 12 males,average age(43.7±17.3 years).All patients had histological diagnosis of ANET(34 carcinoids of appendix and one tubular carcinoid).Majority of tumors have been found incidentally during surgery of:Acute appendicitis(n=15),perforated appendicitis(n=2),ileus(n=3),hysterectomy(n=3),ruptured ovarian cyst(n=2),caecal volvulus(n=1),while 9 patients had diagnosis of appendiceal tumor before the surgery.Seventeen patients had tumor grade(G)G1,12 G2 and 6 G3.The right hemicolectomy was performed in 13,while the rest of the patients had appendectomy only.SRS was done early(2 h)and late(24 h)after i.v.application of 740 MBq technetium-99 m ethylenediamine-N,N’-diacetic acid Hydrazinonicotinyl-Tyr3-Octreotide(technetium-99 m-Tektrotyd,Polatom,Poland).SRS was performed for restaging in all the patients after surgery.RESULTS There were 12 true positive(TP),19 true negative,3 false positive and 1 false negative SRS result.Sensitivity of the method was 92.31%,specificity was 86.36%,positive predictive value was 80.00%,negative predictive value was 95.00%and accuracy 88.57%.Receiver operating characteristics analysis showed that SRS scintigraphy is a good test for detection TP cases[area under the curve of 0.850,95%confidence interval(CI):0.710-0.990,P<001].Single photon emission computed tomography contributed diagnosis in 7 TP findings.In 10 patients Krenning score was 4 and in 2 was 3.In 8 patients SRS significantly changed the management of the patients(in two surgery was repeated,in 4 somatostatin analogues and in two peptide receptor radionuclide therapy).Median progression-free survival in SRS positive patients was 52 months(95%CI:39.7-117.3 mo)while in SRS negative patients it was 60 months(95%CI:42.8-77.1 mo),without statistically significant difference between the two groups(P=0.434).CONCLUSION In conclusion,our results confirmed the value of SRS in the follow-up of the patients with ANET after surgery,if recurrences or metastases are suspected.

Robotically assisted removal of pelvic splenosis fifty-six years after splenectomy: A case report

BACKGROUND‘Splenosis’is defined as the autotransplantation of splenic tissue following trauma or surgery,usually in the form of intraperitoneal nodules.The proliferation of imaging techniques has resulted in increased unexpected discoveries of splenosis nodules,and achieving a differential diagnosis can be challenging.Nuclear medicine studies have been playing an increasingly important role in this process,but the clinical significance of asymptomatic nodules remains uncertain.CASE SUMMARY We present a case of pelvic splenosis in a 73-year-old man diagnosed 56 years after a splenectomy during a computed tomography(CT)follow-up for B-cell lymphoma,presenting intense contrast enhancement of an 18 mm nodule in the right recto-vesical space.18F-fluorodeoxyglucose demonstrated weak metabolic activity.Since histological diagnosis was deemed necessary,the nodule was easily removed with robotically assisted laparoscopy,together with another 6 mm left a paracolic lesion.The latter was previously undiagnosed but retrospectively visible on the CT scan.CONCLUSION In a patient requiring differential diagnosis of splenosis nodules from lymphomarecurrence, the robotic approach provided a safe en bloc removal with shorthospitalization. The Da Vinci Xi robot was particularly helpful because its opticscan be introduced from all ports, facilitating visualization and lysis of multipleintra-abdominal adhesions.

Molecular imaging as a tool for evaluation of COVID-19 sequelae-A review of literature

Coronavirus disease 2019(COVID-19)is caused by the novel viral pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).COVID-19 primarily involves the lungs.Nucleic acid testing based on reverse-transcription polymerase chain reaction of respiratory samples is the current gold standard for the diagnosis of SARS-CoV-2 infection.Imaging modalities have an established role in triaging,diagnosis,evaluation of disease severity,monitoring disease progression,extra-pulmonary involvement,and complications.As our understanding of the disease improves,there has been substantial evidence to highlight its potential for multi-systemic involvement and development of longterm sequelae.Molecular imaging techniques are highly sensitive,allowing noninvasive visualization of physiological or pathological processes at a cellular or molecular level with potential for detection of functional changes earlier than conventional radiological imaging.The purpose of this review article is to highlight the evolving role of molecular imaging in evaluation of COVID-19 sequelae.Though not ideal for diagnosis,the various modalities of molecular imaging play an important role in assessing pulmonary and extra-pulmonary sequelae of COVID-19.Perfusion imaging using single photon emission computed tomography fused with computed tomography(CT)can be utilized as a first-line imaging modality for COVID-19 related pulmonary embolism.^(18)F-fluorodeoxyglucose positron emission tomography(PET)/CT is a sensitive tool to detect multi-systemic inflammation,including myocardial and vascular inflammation.PET in conjunction with magnetic resonance imaging helps in better characterization of neurological sequelae of COVID-19.Despite the fact that the majority of published literature is retrospective in nature with limited sample sizes,it is clear that molecular imaging provides additional valuable information(complimentary to anatomical imaging)with semi-quantitative or quantitative parameters to define inflammatory burden and can be used to guide therapeutic strategies and assess response.However,widespread clinical applicability remains a challenge owing to longer image acquisition times and the need for adoption of infection control protocols.

Creating Knowledge-Based Diagnostic Models by Mining Textual Diagnostic Reports of SPECT Scans

Mining rich semantic information hidden in heterogeneous information network is one of the important tasks of data mining. Generally, a nuclear medicine text consists of the description of disease (i.e., lesions) and diagnostic results. However, how to construct a computer-aided diagnostic model with a large number of medical texts is a challenging task. To automatically diagnose diseases with SPECT imaging, in this work, we create a knowledge-based diagnostic model by exploring the association between a disease and its properties. Firstly, an overview of nuclear medicine and data mining is presented. Second, the method of preprocessing textual nuclear medicine diagnostic reports is proposed. Last, the created diagnostic modes based on random forest and SVM are proposed. Experimental evaluation conducted real-world data of diagnostic reports of SPECT imaging demonstrates that our diagnostic models are workable and effective to automatically identify diseases with textual diagnostic reports.

Immunoscintigraphy with ^99mTc-Besilesomab in Aid to Fusiariosis Detection in Patients with Relapsed Acute Myeloid Leukemia （AML）： A Case Report and Literature Review

The aim of this article is to emphasize the importance of nuclear medicine in fungal infection characterization through a case report. Case： patient female, with AML-M2, hospitalized with fever, dyspnea, nausea, myasthenia, abdominal pain and diarrhea. In the physical examination exacerbated lesion in abdominal wall and subcutaneous nodules in upper and lower limbs. The computed tomography of the chest evinced area of attenuation in ground-glass opacities in the middle lobe, tending to consolidation and bilateral nodular opacities with ground-glass halo which suggested an infiammatory/infectious process of fungal etiology. Immunoscintigraphy with ^99mTc-besilesomab （Scintimun） identified focal infectious processes in activity, scattered over cutaneous and subcutaneous tissues, predominantly in extremities. In blood culture test, there was a growth ofFusarium sp. There is a difficulty in the diagnosis of fungal infections, both in clinical and imaging methods. There is no specific method to reaching the target. In addition, fungal diseases can be divided into focally localized or disseminated infections. There is a greater difficulty in the diagnosis of immunocompromised individuals due to the deficiency of basic defense mechanisms. Scintimun （scintigraphy with besilesomab） is a useful tool of nuclear medicine in the diagnosis of infectious and inflammatory diseases to allow the image of the whole-body and in vivo detection of early pathological and physiological phenomena, even before anatomical alterations occur.

Effect of Two Chinese Medicinal Compounds,Blood-Activating and Water-Draining Medicine,on Tumor Necrosis Factor α and Nuclear Factor κ B Expressions in Rats with Intracerebral Hemorrhage

Objective：To investigate the effect of blood-activating Chinese medicinal compounds and waterdraining Chinese medicinal compounds on tumor necrosis factor alpha（TNF-α）and nuclear factor kappaB（NF-κB）expressions in rats with intracerebral hemorrhage（ICH）at the acute stage,and to monitor their therapeutic effect and mechanism of action on inflammation and cerebral edema.Methods：A rat model of cerebral hemorrhage was achieved by injecting autologous arterial blood into the caudate nucleus.A total of 168 rats were randomly divided into 4 groups：blood-activating medicine group（n=42）,water-draining medicine group（n=42）,sham operated group（n=42）,and the model group（n=42）.A series of brain samples were obtained at days 1,3 and 5 after ICH from rats in all groups.Protein expression levels of TNF-αand NF-κB were measured by immunohistochemical staining and gene expression levels of TNF-αand NF-κB were measured by real-time fluorescent PCR.Results：Compared to the sham operated group,protein expression levels of TNF-αand NF-κB in the model group significantly increased（P〈0.01）.Protein and gene expressions of TNF-αfrom the blood-activating medicine group and water-draining medicine group significantly decreased when compared to those in the model group（P〈0.05）.Meanwhile,compared to the model group,the expression of NF-κB in the blood-activating medicine group significantly decreased（P〈0.05）,while expression of NF-κB in the water-draining medicine group did not differ（P〉0.05）.Conclusions：Blood-activating Chinese medicinal compounds and water-draining Chinese medicinal compounds can alleviate inflammation of peripheral tissue and cerebral edema.However,the blood-activating Chinese medicinal compounds were more effective than the water-draining Chinese medicinal compounds.The possible effective mechanism may be by means of inhibiting the activation of NF-κB so as to suppress the transcription of target genes including gene expression of TNF-α.

Performance tests of a portable thyroid radioiodine meter

Objective:To evaluate the effectiveness of a portable thyroid radioiodine meter in on-site monitoring to enhance the monitoring precision of radioiodine inhaled by nuclear medicine staff and patients.Methods:A portable thyroid radioiodine meter was developed to measure the 131I activity in the thyroid.Performance tests of the portable thyroid radioiodine meter were conducted using calibration sources and testing methodologies adhering to national metrological standards.Results:The thyroid radioiodine meter exhibited integral non-linearity,8-h measurement stability,measurement linearity,and an energy resolution of 0.42%,1.05%,1.56%,and 7.11%,respectively for ^(137)Cs at 661.66 keV.Additionally,its minimum detectable activity for ^(131)I at 364.49 keV was approximately 22 Bq(10 min).Conclusion:The developed thyroid radioiodine meter features elevated performance and great potential for application in nuclear medicine and monitoring of responses to nuclear or radiological emergencies.

Nuclear medical molecular imaging of tumor angiogenesis： current status and future prospects

Objective To review the current status and progress on nuclear medical molecular imaging of angiogenesis. Data sources A literature search was performed in Medline and PubMed published in English up to May 31, 2012. The search terms were molecular imaging, nuclear medicine and angiogenesis. Study selection Articles studying molecular imaging of angiogenesis using radionuclide were selected and reviewed. Results Molecular imaging has been used for studying angiogenesis by targeting integrin aVI33, VEGF/VEGFR, and matrix metalloproteinases （MMPs） with radionuclide-labeled tracers. The technology has been shown to be able to assess the angiogenesis status and/or predict the efficacy of anti-angiogenic therapy. Future directions of the research on the molecular imaging of angiogenesis include development of new tracers with better tumor targeting efficacy, desirable pharmacokinetics, and easy translation to clinical applications. Conclusion Advances in molecular imaging of angiogenesis using radioculcide will make the technology a valuable tool for personalized anti-angiogenesis treatment.

Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury

Acute kidney injury(AKI)leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs.Here,a series of polyvinylpyrrolidone(PVP)-curcumin nanoparticles(PCurNP)are designed to meet the renal excretion threshold(~45 kDa),presenting a controllable delivery nanosystem for kidney targeting.Renal accumulation of the relatively small nanoparticles,^(89)Zr-PCurNP M10 with the diameter between 5 and 8 nm,is found to be 1.7 times and 1.8 times higher than the accumulation of^(89)Zr-PCurNP M29(20-50 nm)and M40(20-50 nm)as revealed by PET imaging.Furthermore,serum creatinine analysis,kidney tissues histology,and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI.Herein,PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

Panax notoginseng Saponins Protect Kidney from Diabetes by Up-regulating Silent Information Regulator 1 and Activating Antioxidant Proteins in Rats

Objective： To explore the mechanism of the protective effects of Panax notoginseng saponins（PNS） on kidney in diabetic rats. Methods： Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/（kg·day） and PNS-200 mg/（kg·day） groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7（BMP-7）. Silent information regulator 1（SIRT1） was silenced in rat mesangial cells by RNA interference. The mR NA expressions of SIRT-1, monocyte chemoattractant protein-1（MCP-1）, transforming growth factor β1（TGF-β1） and plasminogen activator inhibitor-1（PAI-1） were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB（NF-κB） P65 were determined by western blotting. The concentration of MCP-1, TGF-β1 and malondialdehyde（MDA） in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase（SOD） was detected by the classical method of nitrogen and blue four. Results： In diabetic model rats, PNS could not only reduce blood glucose and lipid（P〈0.01）, but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1（P〈0.01） and in turn suppress the transcription of TGF-β1（P〈0.05） and MCP-1（P〈0.05）. PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated（P〈0.05） and SOD was up-regulated（P〈0.01）, which were both induced by SIRT1 up-regulation. Conclusions： PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-β1, as well as activating antioxidant proteins.