Multiscale Imaging to Monitor Functional SHED-Supported Engineered Vessels.

Regeneration of orofacial tissues is hampered by the lack of adequate vascular supply. Implantation of in vitro engineered, prevascularized constructs has emerged as a strategy to allow the rapid vascularization of the entire graft. Given the angiogenic properties of dental pulp stem cells, we hereby established a preclinical model of prevascularized constructs loaded with stem cells from human exfoliating deciduous teeth (SHED) in a 3-dimensional-printed material and provided a functional analysis of their in vivo angiogenesis, vascular perfusion, and permeability. Three different cell-loaded collagen hydrogels (SHED-human umbilical vein endothelial cell [HUVEC], HUVEC with SHED-conditioned medium, and SHED alone) were cast in polylactic acid (PLA) grids and ectopically implanted in athymic mice. At day 10, in vivo positron emission tomography (PETscan) revealed a significantly increased uptake of radiotracer targeting activated endothelial cells in the SHED-HUVEC group compared to the other groups. At day 30, ex vivo micro-computed tomography imaging confirmed that SHED-HUVEC constructs had a significantly increased vascular volume compared to the other ones. Injection of species-specific lectins analyzed by 2-photon microscopy demonstrated blood perfusion of the engineered human vessels in both prevascularized groups. However, in vivo quantification showed increased vessel density in the SHED-HUVEC group. In addition, coinjection of fluorescent lectin and dextran revealed that prevascularization with SHED prevented vascular leakage, demonstrating the active role of SHED in the maturation of human-engineered microvascular networks. This preclinical study introduces a novel PLA prevascularized and implantable construct, along with an array of imaging techniques, to validate the ability of SHED to promote functional human-engineered vessels, further highlighting the interest of SHED for orofacial tissue engineering. Furthermore, this study validates the use of PETscan for the early detection of in vivo angiogenesis, which may be applied in the clinic to monitor the performance of prevascularized grafts.

Nuclear Medicine Imaging Techniques in Glioblastomas.

Glioblastomas are the most common primary malignant grade 4 tumors of the central nervous system (CNS). The treatment and management of such tumors requires a multidisciplinary approach and nuclear medicine techniques play an important role in this process. Glioblastoma, which recurs despite current treatments and becomes resistant to treatments, is among the tumors with the lowest survival rate, with a survival rate of approximately 8 months. Currently, the standard treatment of glioblastoma is adjuvant chemoradiotherapy after surgical resection. There have been many recent advances in the field of Nuclear Medicine in glioblastoma. PET scans are critical in determining tumor localization, pre-surgical planning, evaluation of post-treatment response and detection of recurrence. Advances in the treatment of glioblastoma and a better understanding of the biological characteristics of the disease have contributed to the development of nuclear medicine techniques. This review, in addition to other studies, is intended as a general imaging summary guide and includes some new expressions discovered in glioblastoma. This review discusses recent advances in nuclear medicine in glioblastoma.

Radiolabeled Probes from Derivatives of Natural Compounds Used in Nuclear Medicine.

Natural compounds are important precursors for the synthesis of new drugs. The development of novel molecules that are useful for various diseases is the main goal of researchers, especially for the diagnosis and treatment of many diseases. Some pathologies need to be treated with radiopharmaceuticals, and, for this reason, radiopharmaceuticals that use the radiolabeling of natural derivates molecules are arousing more and more interest. Radiopharmaceuticals can be used for both diagnostic and therapeutic purposes depending on the radionuclide. ß+- and gamma-emitting radionuclides are used for diagnostic use for PET or SPECT imaging techniques, while α- and ß--emitting radionuclides are used for in metabolic radiotherapy. Based on these assumptions, the purpose of this review is to highlight the studies carried out in the last ten years, to search for potentially useful radiopharmaceuticals for nuclear medicine that use molecules of natural origin as lead structures. In this context, the main radiolabeled compounds containing natural products as scaffolds are analyzed, in particular curcumin, stilbene, chalcone, and benzofuran. Studies on structural and chemical modifications are emphasized in order to obtain a collection of potential radiopharmaceuticals that exploit the biological properties of molecules of natural origin. The radionuclides used to label these compounds are 68Ga, 44Sc, 18F, 64Cu, 99mTc, and 125I for diagnostic imaging.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

BACKGROUND: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. MAIN BODY: This selection of highlights provides commentary on 19 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. CONCLUSION: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.

Radiotracer Innovations in Breast Cancer Imaging: A Review of Recent Progress.

This review focuses on the pivotal role of radiotracers in breast cancer imaging, emphasizing their importance in accurate detection, staging, and treatment monitoring. Radiotracers, labeled with radioactive isotopes, are integral to various nuclear imaging techniques, including positron emission tomography (PET) and positron emission mammography (PEM). The most widely used radiotracer in breast cancer imaging is 18F-fluorodeoxyglucose (18F-FDG), which highlights areas of increased glucose metabolism, a hallmark of many cancer cells. This allows for the identification of primary tumors and metastatic sites and the assessment of tumor response to therapy. In addition to 18F-FDG, this review will explore newer radiotracers targeting specific receptors, such as estrogen receptors or HER2, which offer more personalized imaging options. These tracers provide valuable insights into the molecular characteristics of tumors, aiding in tailored treatment strategies. By integrating radiotracers into breast cancer management, clinicians can enhance early disease detection, monitor therapeutic efficacy, and guide interventions, ultimately improving patient outcomes. Ongoing research aimed at developing more specific and sensitive tracers will also be highlighted, underscoring their potential to advance precision medicine in breast cancer care.

Advancing stroke diagnosis and management through nuclear medicine: a systematic review of clinical trials.

Introduction: Despite advancements in stroke care, challenges persist in timely triage and treatment initiation to prevent the burden of stroke-related disabilities. Although nuclear medicine has shown promise, no imaging technique has yet provided a sufficiently rapid, precise, and cost-effective approach to routine stroke management. This study aims to review the clinical application of nuclear medicine in stroke diagnosis and treatment. Methods: A systematic search of the Cochrane, EU Clinical Trials Register, ISRCTN, the International Stroke Trial, and the ClinicalTrials.gov database was conducted to find all registered trials reporting nuclear medicine's clinical applications in stroke up to June 07, 2024. Results: Among the 220 screened trials, 51 (36 interventional; 15 observational) met the eligibility criteria. Participants were older than 18 years old, with only six studies including pediatric under 17 years old, with a total of 11,262 stroke (9,232 ischemic; 2,030 haemorrhagic) participants. The bias risk varied across trials but remained mostly low to moderate. Discussion: The review highlighted nuclear medicine's significant contributions to stroke diagnosis and management, notably through mobile stroke units, pre-hospital acute stroke magnetic resonance image (MRI) based biomarkers, and MRI-based stroke mechanisms for 4D flow nuclear imaging. These advancements have generally reduced treatment delays and enhance clinical outcomes post-stroke. Specifically, radiopharmaceutical radiotracers can effectively discriminate between strokes and mimics, particularly in high-risk patients. Integrating novel positron emission tomography (PET) radiotracer 18F glycoprotein 1 and radionuclide angiography may improve sensitivity and specificity in thrombi detection for decisions regarding stenting or carotid endarterectomy, and the single-photon emission computed tomography and PET integration with ferumoxytol radiotracer-enhanced MRI enables functional imaging for evaluating cerebral perfusion, metabolic activity, and neuroinflammatory markers post-stroke. Overall, the integration of nuclear medicine into multimodal imaging equipment like computed-tomography PET and MRI-PET offers a more comprehensive picture of the brain. Nevertheless, further research is needed on novel stroke imaging techniques and standardization across stroke centers for optimal performance. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024541680, identifier PROSPERO CRD(42024541680).

A unique intersection: Exploring an exophytic, pedunculated hepatic hemangioma with gastric connection in a case report.

Hepatic hemangiomas are commonly benign liver tumors, typically asymptomatic and predominantly located in the right lobe. This case report details an exceptional instance of a left-lobe hepatic hemangioma manifesting as an exophytic, pedunculated mass resembling a gastric tumor. A 77-year-old woman with a history of melanoma presented with a mass incidentally discovered during evaluations for chest pain. Advanced imaging techniques, including computed tomography (CT) and endoscopic ultrasound (EUS), identified this mass as a benign, pedunculated hemangioma extending from the left hepatic lobe toward the gastric fundus. Given the tumor's benign nature and the patient's lack of symptoms, a conservative management approach was adopted. This case emphasizes the importance of accurate imaging and diagnostic assessment in managing atypical hepatic hemangiomas, highlighting the need to carefully consider rare growth patterns and locations in differential diagnoses to avoid unnecessary interventions. Such cases reinforce the complexity of diagnosing and managing unusual presentations of common benign tumors.

Developments in radionanotheranostic strategies for precision diagnosis and treatment of prostate cancer.

BACKGROUND: Prostate Cancer (PCa) is the second most diagnosed urological cancer among men worldwide. Conventional methods used for diagnosis of PCa have several pitfalls which include lack of sensitivity and specificity. On the other hand, traditional treatment of PCa poses challenges such as long-term side effects and the development of multidrug resistance (MDR). MAIN BODY: Hence, there is a need for novel PCa agents with the potential to lessen the burden of these adverse effects on patients. Nanotechnology has emerged as a promising approach to support both early diagnosis and effective treatment of tumours by ensuring precise delivery of the drug to the targeted site of the disease. Most cancer-related biological processes occur on the nanoscale hence application of nanotechnology has been greatly appreciated and implemented in the management and therapeutics of cancer. Nuclear medicine plays a significant role in the non-invasive diagnosis and treatment of PCa using appropriate radiopharmaceuticals. This review aims to explore the different radiolabelled nanomaterials to enhance the specific delivery of imaging and therapeutic agents to cancer cells. Thereafter, the review appraises the advantages and disadvantages of these modalities and then discusses and outlines the benefits of radiolabelled nanomaterials in targeting cancerous prostatic tumours. Moreover, the nanoradiotheranostic approaches currently developed for PCa are discussed and finally the prospects of combining radiopharmaceuticals with nanotechnology in improving PCa outcomes will be highlighted. CONCLUSION: Nanomaterials have great potential, but safety and biocompatibility issues remain. Notwithstanding, the combination of nanomaterials with radiotherapeutics may improve patient outcomes and quality of life.

Analysis of progression of number and structure of scans performed using PET, PET/ CT and PET/ MRI in the Czech Republic in 2013- 2021.

BACKGROUND: Positron emission tomography (PET) is a state-of-the-art diagnostic method of nuclear medicine, used for diagnostics of many pathological states in the organism, first and foremost in oncological issues. The first analysis of utilization and potential utilization of PET in the Czech Republic was published in 2013. In the following years, there was a sharp increase in a number of PET/CT and PET/MRI scanners in the country; in 2013-2021, it doubled. Simultaneously with the increase in scans performed, the range of available radiopharmaceuticals also broadened. MATERIAL AND METHODS: The study analyses the numbers and structure of PET, PET/CT and PET/MRI scans in the 2013-2021 period, using the pseudonymized data acquired from the General Health Insurance Company of the Czech Republic. The data was evaluated through a series of qualitative and quantitative indicators (number of scans performed, structure of diagnoses, use of different tracers, and availability of a scan for a patient). RESULTS: In the observed interval of time, the number of scans performed practically doubled, both thanks to more scanners installed and more radiopharmaceuticals available. The percentage of oncological and non-oncological scans remains more or less the same. Nevertheless, the regional differences in a number of scans performed persist, as does the availability of the scan for patients. CONCLUSION: PET is still a dynamically developing molecular imaging method in the Czech Republic. The analysis of a number and structure of scans performed offers a priceless overview of the development of the method over the years, in regard to diagnoses, utilization of individual radiopharmaceuticals or geographic distribution of scans performed. The observed findings are a motivation for further analyses.

Performance of [18F]FDG PET/CT in Diagnosing Cyst Infections in Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and a Bivariate Meta-Analysis.

BACKGROUND: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has been suggested as a useful imaging method for diagnosing cyst infections in patients with autosomal dominant polycystic kidney disease (ADPKD). The aim of this article is to provide evidence-based data in this setting. METHODS: A systematic literature review (exploring several bibliographic databases) and a bivariate meta-analysis were carried out to calculate the pooled diagnostic performance of [18F]FDG PET/CT in diagnosing probable cyst infection in ADPKD. RESULTS: Ten studies (282 PET/CT scans and 249 patients) were included in the analysis. The pooled sensitivity and specificity of [18F]FDG PET/CT in this setting were 84.6% (95% confidence interval: 75.4-90.7) and 94.9% (95% confidence interval: 72.6-99.2), respectively, without statistical heterogeneity or significant publication bias. [18F]FDG PET/CT significantly changed patient management in more than half of ADPKD patients with suspected cyst infection. CONCLUSIONS: [18F]FDG PET/CT has high performance in diagnosing probable cyst infections in ADPKD patients with an impact on management in the majority of patients. Although more studies are warranted, the provided evidence-based data are an important step towards the integration of [18F]FDG PET/CT in clinical and diagnostic guidelines on probable cyst infection in ADPKD patients.

Incidence of Persistence and Recurrence of Differentiated Thyroid Cancer in Post-surgical Cases From a Tertiary Care Hospital in Dubai, United Arab Emirates.

Background Despite the excellent prognosis of differentiated thyroid carcinoma, recurrence remains a major concern. However, the persistence of thyroid cancer post-thyroidectomy is not uncommon. We aimed to characterise patients who underwent re-operative surgery for differentiated thyroid carcinoma and analyse the percentage of re-operations that truly were for "recurrent" disease versus the management of persistent disease. Methods We conducted a retrospective review of the hospital database, analysing patients who visited the nuclear medicine department at Mediclinic City Hospital, a tertiary care hospital in Dubai, United Arab Emirates, between 2015 and 2022. The study included patients with differentiated thyroid carcinoma who underwent re-operations after total thyroidectomy. Recurrence was defined as the development of disease after a patient had undetectable thyroglobulin and negative radiological scans within one year of the first surgery. Cases were categorised as "recurrent", "persistent", or "unable to classify" in the event of missing data. Results Out of 836 patients diagnosed with differentiated thyroid carcinoma who visited the nuclear medicine department, 71 underwent re-operations. The mean age of these patients was 44.4 years (CI 41.7-47.0), of whom 78.9% were females. Almost half (46.5%) underwent re-operations within the first year, and 98.6% were diagnosed with papillary thyroid carcinoma. We were able to classify 63.4% of cases (n=45) as persistent disease, while 24 cases were categorised as "unable to classify". Only two cases met the criteria for recurrent disease. Conclusion The majority of cases previously classified as "recurrent" in differentiated thyroid carcinoma were found to be a persistent disease, possibly indicating inadequate therapy. Further research may be required to explore the reasons behind this eye-opening rate of disease persistence. This highlights an area for improvement in the management and future outcomes of differentiated thyroid carcinoma patients.

A Rare Case of Urinary Bladder Leiomyoma Invading Urachal Remnant Managed With Robotic Partial Cystectomy.

Leiomyoma is a rare benign tumour of the urinary bladder. Typically, bladder leiomyomas are treated with transurethral resection, which yields favourable results. We present a clinical case of a 29-year-old man with a symptomatic bladder tumour, initially diagnosed on flexible cystoscopy and CT scan. Subsequent transurethral resection and MRI scan confirmed a transmural bladder leiomyoma invading the urachal remnant. The patient was subsequently treated with robotic partial cystectomy. The presentation and management, including imaging and histopathology results, are discussed with a brief review of the literature.

Actinium-225 in Targeted Alpha Therapy.

The utilization of actinium-225 (225Ac) radionuclides in targeted alpha therapy for cancer was initially outlined in 1993. Over the past two decades, substantial research has been conducted, encompassing the establishment of 225Ac production methods, various preclinical investigations, and several clinical studies. Currently, there is a growing number of compounds labeled with 225Ac that are being developed and tested in clinical trials. In response to the increasing demand for this nuclide, production facilities are either being built or have already been established. This article offers a concise summary of the present state of clinical advancements in compounds labeled with 225Ac. It outlines various processes involved in the production and purification of 225Ac to cater to the growing demand for this radionuclide. The article examines the merits and drawbacks of different procedures, delves into preclinical trials, and discusses ongoing clinical trials.

How anatomical impairments found on CT affect perfusion percentage assessed by SPECT/CT scan?

AIM: CT images can identify structural and opacity alterations of the lungs while nuclear medicine's lung perfusion studies show the homogeneity (or lack of) of blood perfusion on the organ. Therefore, the use of SPECT/CT in lung perfusion scintigraphies can help physicians to assess anatomical and functional alterations of the lungs and to differentiate between acute and chronic disease. OBJECTIVE: To develop a computer-aided methodology to quantify the total global perfusion of the lungs via SPECT/CT images and to compare these results with parenchymal alterations obtained in CT images. METHODS: 39 perfusion SPECT/CT images collected retrospectively from the Nuclear Medicine Facility of Botucatu Medical School's Clinics Hospital in São Paulo, Brazil, were analyzed. Anatomical lung impairments (emphysema, collapsed and infiltrated tissue) and the functional percentage of the lungs (blood perfusion) were quantified from CT and SPECT images, with the aid of the free, open-source software 3D Slicer. The results obtained with 3D Slicer (3D-TGP) were also compared to the total global perfusion of each patient's found on their medical report, obtained from visual inspection of planar images (2D-TGP). RESULTS: This research developed a novel and practical methodology for obtaining lungs' total global perfusion from SPECT/CT images in a semiautomatic manner. 3D-TGP versus 2D-TGP showed a bias of 7% with a variation up to 67% between the two methods. Perfusion percentage showed a weak positive correlation with infiltration (p = 0.0070 and ρ = 0.43) and collapsed parenchyma (p = 0.040 and ρ = 0.33). CONCLUSIONS: This research brings meaningful contributions to the scientific community because it used a free open-source software to quantify the lungs blood perfusion via SPECT/CT images and pointed that the relationship between parenchyma alterations and the organ's perfusion capability might not be so direct, given compensatory mechanisms.

Automatic Classification of Conclusions from Multi-Tracer Reports of PET Brain Imaging in Cognitive Impairment.

The goal of this paper is to build an automatic way to interpret conclusions from brain molecular imaging reports performed for investigation of cognitive disturbances (FDG, Amyloid and Tau PET) by comparing several traditional machine learning (ML) techniques-based text classification methods. Two purposes are defined: to identify positive or negative results in all three modalities, and to extract diagnostic impressions for Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD), Lewy Bodies Dementia (LBD) based on metabolism of perfusion patterns. A dataset was created by manual parallel annotation of 1668 conclusions of reports from the Nuclear Medicine and Molecular Imaging Division of Geneva University Hospitals. The 6 Machine Learning (ML) algorithms (Support Vector Machine (Linear and Radial Basis function), Naive Bayes, Logistic Regression, Random Forrest, and K-Nearest Neighbors) were trained and evaluated with a 5-fold cross-validation scheme to assess their performance and generalizability. The best classifier was SVM showing the following accuracies: FDG (0.97), Tau (0.94), Amyloid (0.98), Oriented Diagnostic (0.87 for a diagnosis among AD, FTD, LBD, undetermined, other), paving the way for a paradigm shift in the field of data handling in nuclear medicine research.

[Radiation Dose Considerations for Breast Sonographers Following 99mTc-HMDP Bone Scan Administration].

PURPOSE: Patients who were administered radiopharmaceuticals can be a source of radiation exposure to sonographers. This study aimed to identify factors associated with radiation exposure to breast sonographers from patients administered radiopharmaceuticals for bone scanning. METHODS: The exposure dose of six sonographers was measured during breast sonography in 59 patients administered 99mTc-HMDP. We predicted the following factors to be related to exposure dose: time interval between administration and sonography, sonography examination time, estimated radioactivity at sonography, sonographer's years of experience, and patients' clinical data (age, renal function and surgical procedure). Spearman's rank correlation coefficient was used to examine the relationship between radiation dose and the aforementioned factors. RESULTS: The mean±standard deviation of the exposure dose for the sonographers was 9.3±3.8 µSv. The time interval between administering the radiopharmaceutical agent and sonography, the sonography examination time and estimated radioactivity at sonography were found to be factors related to the exposure of the sonographer. The exposure dose increased as a function of the shorter time interval, longer examination time and higher estimated radioactivity at sonography. CONCLUSION: The time interval between drug administration and sonography, sonography examination time and estimated radioactivity at sonography contributed to the increased dose to breast sonographers. Although we considered that the exposure dose of sonographers would not possibly exceed the dose limit in the present study, we suggested that radiological technologists need to educate the physicians requesting sonography, and the sonographers about the radiation exposure in nuclear medicine.

Use of real-time electronic extremity dosimeters for monitoring and optimisation of radiopharmacy technique.

Radiopharmacy staff members are subject to extremity radiation doses, particularly to the fingertips. Dosemeters, such as, thermoluminescent detectors (TLDs) are currently used for monitoring fingertip doses. This study aimed to use real-time dosemeters to monitor radiopharmacy extremity doses to identify specific procedural steps associated with higher fingertip doses and, subsequently, reduce dose through promotion of optimised radiation protection practises. Five radiopharmacy operators were monitored using an ED3 active extremity dosemeter with a detector attached to each tip of the index fingers. Dose rate and accumulated dose data were matched to the handled radioactivity data, of99mTc-labelled radiopharmaceuticals only, with the dose per activity (µSv MBq-1) calculated for each step. Once baseline dose data was established, an educational session identified technique adjustments toward improved radiation protection. A subsequent monitored session was undertaken with the dose data compared to quantify changes in operator doses. Radiopharmacy steps which significantly contributed to extremity doses were identified. The average accumulated dose per activity across all procedural steps for the99mTc-labelled radiopharmaceuticals for all operators before the educational session was 0.042 ± 0.045µSv MBq-1and 0.042 ± 0.041µSv MBq-1(n= 89) for non-dominant and dominant index fingertips, respectively, and 0.030 ± 0.044µSv MBq-1and 0.031 ± 0.032µSv MBq-1(n= 97), respectively, afterwards. Overall, there was an average 40.7% reduction in the total extremity dose received after the educational session. Real-time electronic extremity dosemeters for monitoring radiopharmacy extremity dose presented as a useful tool for incorporation into radiation protection education and training, towards optimised radiopharmacy technique.

Radioimmunotheragnosis in Cancer Research.

The combination of immunoPET-where an antibody (Ab) is labeled with an isotope for PET imaging-and radioimmunotherapy (RIT), using the same antibody with a therapeutic isotope, offers significant advantages in cancer management. ImmunoPET allows non-invasive imaging of antigen expression, which aids in patient selection for subsequent radioimmunotherapy. It also facilitates the assessment of tumor response to therapy, allowing for treatment adjustments if necessary. In addition, immunoPET provides critical pharmacokinetic data, including antibody biodistribution and clearance rates, which are essential for dosimetry calculations and treatment protocol optimization. There are still challenges to overcome. Identifying appropriate target antigens that are selectively expressed on cancer cells while minimally expressed on normal tissues remains a major hurdle to reduce off-target toxicity. In addition, it is critical to optimize the pharmacokinetics of radiolabeled antibodies to maximize tumor uptake and minimize normal tissue uptake, particularly in vital organs such as the liver and kidney. This approach offers the potential for targeted and personalized cancer therapy with reduced systemic toxicity by exploiting the specificity of monoclonal antibodies and the cytotoxic effects of radiation. However, further research is needed to address remaining challenges and to optimize these technologies for clinical use.

Combining Nuclear Medicine With Other Modalities: Future Prospect for Multimodality Imaging.

This meeting report summarizes a consultants meeting that was held at International Atomic Energy Agency Headquarters, Vienna, in July 2022 to provide an update on the development of multimodality imaging by combining nuclear medicine imaging agents with other nonradioactive molecular probes and/or biomedical imaging techniques.