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Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e.g. myelosuppression). Since the introduction of Iodine-131 as a targeted therapy in thyroid cancer, several radiopharmaceuticals have been widely used. These include antibodies and peptides targeting specific epitopes on cancer cells. Among therapeutic bone seeking agents, radium-223 ( 223 Ra) stands out as it results in survival gains in patients with castration-resistant prostate cancer and symptomatic bone metastases. The therapeutic use of radiopharmaceuticals in elderly cancer patients specifically has received little attention. In elderly prostate cancer patients, there may be advantages in radionuclides' ease of use and relative lack of toxicity compared with cytotoxic and cytostatic drugs. When using radionuclide therapies, close coordination between oncology and nuclear medicine is needed to ensure safe and effective use. Bone marrow reserve has to be considered. As most radiopharmaceuticals are cleared renally, dose adjustment may be required in the elderly. However, compared with younger patients there is less, if any, concern about adverse long-term radiation effects such as radiation-induced second cancers. Issues regarding the safety of medical staff, care givers and the wider environment can be managed by current precautions., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: To assess in a phantom and in a clinical study the influence of different reconstruction parameters on quantitative SPECT/CT values in the assessment of cardiac transthyretin amyloidosis (ATTR-CA)., Method: A hybrid SPECT/CT camera with a proprietary software for SPECT/CT-based quantification of myocardial uptake of 99m Tc-DPD was used. Images were reconstructed with 6 different protocols, differing in iterations, subset and Gaussian filter. Quantitative values were tested in phantom and clinical studies across different reconstruction protocols. Values were automatically calculated both as kBq/ml and as maximum, mean and peak standardized uptake value (SUV)., Results: The standard parameters provided by the manufacturer (reconstruction 1) yielded higher accuracy in quantifying, with measuring 97.1% of the expected activity in the phantom. Reconstructions with higher Gaussian filter caused a systematic underestimation of quantified values of 27.2% (p < 0.01). Results were replicated in the clinical study consisting of 155 patients with suspected ATTR-CA, wherein changing the number of iterations and subsets was not associated with a statistically significant difference in quantitative values compared to reconstruction 1, while a higher Gaussian filter caused inaccurate quantification with up to 24% of difference measured., Conclusion: Different reconstruction parameters can impact quantitative values on 99m Tc-DPD SPECT/CT. Therefore, parameters should be maintained consistently across different acquisitions and different centres., Competing Interests: Declarations Competing interests The authors declare no competing interests. Disclosures Robin Schepers has received speaker honoraria from Siemens. Christoph Gräni receives funding from the Swiss National Science foundation, InnoSuisse, CAIM foundation, GAMBIT foundation and Novartis biomedical research foundation, outside of the submitted work. Axel Rominger has received research support and speaker honoraria from Siemens. Federico Caobelli is currently supported by a research grant by Siemens Healthineers and receives speakers Honoraria by Bracco AG and Pfizer AG for matters not related to the present manuscript. All other authors have no competing interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Rheumatoid arthritis (RA) is an inflammatory chronic disease characterized by inflammation, pain, swelling and disability, and radiosynovectomy is one of the disease treatment lines. In this study, the possibility of providing rhenium-186/rhenium-188 chitosan radiopharmaceuticals, optimization of conditions for their production and bio-distribution are reported., Objective: In order to build perrhenic acid for labeling, natural rhenium was exposed to radiation. Radionuclidic and radiochemical purities of (186/188Re)-NaReO4 were examined by gamma spectroscopy and paper chromatography methods, respectively., Methods: Labeling of chitosan with rhenium was done in different acidic situations. The radiochemical purity 186/188Re-chitosan was applied by radio thin layer chromatography (RTLC). Lastly, the bio-distribution of the radiolabeled chitosan was studied in various organs after intra articular injection of the complex to lab rats. Gamma spectrometry confirmed the high rhenium radionuclidic purity. Chromatography results showed that perrhenic acid was produced with purity greater than 97% and rhenium chitosan labeling was done over 98% in pH = 3. Dissection results showed a high bio-distribution of 186/188Re-chitosan after injection into the joint with no leakage to surrounding organs., Conclusion: According to the results, there is a possibility of labeling rhenium with chitosan in very high radiochemical purity. Regarding the high retention of these radiopharmaceuticals in joints with no leakage to surrounding organs, 186/188Re-chitosan can be applied as new radiosynovectomy drugs for rheumatoid arthritis treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [(99m)Tc(MIBI)₆]⁺ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [(99m)Tc(MIBI)₆]⁺ since impurities such as (99m)Tc-reduced-hydrolyzed (RH), (99m)TcO(4)(-) and [(99m)Tc(cysteine)₂]⁻ complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

Background: Increased positron emission tomography (PET) scanner z-axis coverage provides an opportunity in pediatrics to reduce dose, anesthesia, or repeat scans due to motion., Objective: Recently, our digital PET scanner was upgraded from a 25-cm to a 30-cm z-axis coverage. We compare the two systems through National Electrical Manufacturing Association (NEMA) testing and evaluation of paired images from patients scanned on both systems., Materials and Methods: NEMA testing and a retrospective review of pediatric patients who underwent clinically indicated 18F-fluorodeoxyglucose (FDG) PET computed tomography (PET/CT) on both systems with unchanged acquisition parameters were performed. Image quality was assessed with liver signal to noise ratio (SNR-liver) and contrast to noise ratio (CNR) in the thigh muscle and liver with results compared with an unpaired t-test. Three readers independently reviewed paired (25 cm and 30 cm) images from the same patient, blinded to scanner configuration., Results: Expansion to 30 cm increased system sensitivity to 29.8% (23.4 cps/kBq to 30.4 cps/kBq). Seventeen patients (6 male/11 female, median age 12.5 (IQR 8.3-15.0) years, median weight 53.7 (IQR 34.2-68.7) kg) were included. SNR-liver and CNR increased by 35.1% (IQR 19.0-48.4%) and 43.1% (IQR 6.2-50.2%) (P-value <0.001), respectively. All readers preferred images from the 30-cm configuration. A median of 1 (IQR 1-1) for fewer bed positions was required with the 30-cm configuration allowing a median of 91 (IQR 47-136) s for shorter scans., Conclusion: Increasing z-axis coverage from 25 to 30 cm on a current-generation digital PET scanner significantly improved PET system performance and patient image quality, and reduced scan duration., (© 2024. The Author(s).)

Background: Nuclear medicine has made enormous progress in the past decades. However, there are still significant inequalities in patient access among different countries, which could be mitigated by improving access to and availability of radiopharmaceuticals. Main body: This paper summarises major considerations for a suitable pharmaceutical regulatory framework to facilitate patient access to radiopharmaceuticals. These include the distinct characteristics of radiopharmaceuticals which require dedicated regulations, considering the impact of the variable complexity of radiopharmaceutical preparation, personnel requirements, manufacturing practices and quality assurance, regulatory authority interfaces, communication and training, as well as marketing authorisation procedures to ensure availability of radiopharmaceuticals. Finally, domestic and regional supply to ensure patient access via alternative regulatory pathways, including in-house production of radiopharmaceuticals, is described, and an outlook on regulatory challenges faced by new developments, such as the use of alpha emitters, is provided. Conclusions: All these considerations are an outcome of a dedicated Technical Meeting organised by the IAEA in 2023 and represent the views and opinions of experts in the field, not those of any regulatory authorities. [ABSTRACT FROM AUTHOR]

The numbers of diagnostic and therapeutic nuclear medicine agents under investigation are rapidly increasing. Both novel emitters and novel carrier molecules require careful selection of measurement procedures. This document provides guidance relevant to dosimetry for first-in human and early phase clinical trials of such novel agents. The guideline includes a short introduction to different emitters and carrier molecules, followed by recommendations on the methods for activity measurement, pharmacokinetic analyses, as well as absorbed dose calculations and uncertainty analyses. The optimal use of preclinical information and studies involving diagnostic analogues is discussed. Good practice reporting is emphasised, and relevant dosimetry parameters and method descriptions to be included are listed. Three examples of first-in-human dosimetry studies, both for diagnostic tracers and radionuclide therapies, are given., (© 2024. The Author(s).)

Abstract This is a position paper of the Radiopharmacy Committee of the EANM (European Association of Nuclear Medicine) addressing toxicology studies for application of new diagnostic and therapeutic radiopharmaceuticals (RP) that are not approved (i.e., not having a marketing authorization or a monograph in the European Pharmacopoeia), excluding endogenous and ubiquitous substances in humans. This paper discusses the requirements for clinical trials with radiopharmaceuticals for clinical research applications, not necessarily intended to aim at a marketing authorization. If marketing authorization is intended, scientific advice of the competent authorities is mandatory and cannot be replaced by this position paper. The position paper reflects the view of the Radiopharmacy Committee of the EANM and can be used as a basis for discussions with the responsible authorities.

Purpose: To evaluate the role of semiquantitative parameters derived from 18 F-FDG PET/CT in characterizing pediatric malignant kidney tumors., Methods: 54 children with pathologically confirmed renal malignancies who underwent pretreatment 18 F-FDG PET/CT were retrospectively reviewed. Association between PET-derived semiquantitative parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and tumor histology, disease stage, and loss of heterozygosity were analyzed., Results: Of the 54 patients, 43 had Wilms tumor (WT), 4 had clear cell sarcoma of the kidney (CCSK), 3 had rhabdoid tumor of kidney, 2 had renal cell carcinoma, and 2 had congenital mesoblastic nephroma. 18 F-FDG PET/CT detected all primary renal tumors, with SUVmax ranging from 1.2 to 14.5. PET-derived parameters showed no significant differences among different tumor types, except for CCSK, which exhibited lower FDG uptake compared to WT (SUVmax 3.60 ± 1.02 vs. 6.10 ± 2.25, p = 0.034). Higher MTV, TLG, and lactate dehydrogenase were associated with stage IV disease. ROC analysis showed that TLG had the highest AUC (0.931) for predicting stage IV disease in the whole cohort, while SUVmax had the highest AUC (0.867) for predicting stage IV and V in WT. Furthermore, Children with 1q gain exhibited higher MTV in WT (447 ± 354 vs. 207 ± 189, p = 0.041)., Conclusion: PET-derived semiquantitative parameters highly associated with disease stage both in the overall cohort of renal malignancies and specifically in the WT group. Additionally, volumetric metabolic indices might provide further insights into loss of heterozygosity in children with WT., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study. Author disclosures: Compliance with ethical standards. Conflict of interest: The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In patients with drug-resistant epilepsy, difficulties in identifying the epileptogenic zone are well known to correlate with poorer clinical outcomes post-surgery. The integration of PET and MRI in the presurgical assessment of pediatric patients likely improves diagnostic precision by confirming or widening treatment targets. PET and MRI together offer superior insights compared to either modality alone. For instance, PET highlights abnormal glucose metabolism, while MRI precisely localizes structural anomalies, providing a comprehensive understanding of the epileptogenic zone. Furthermore, both methodologies, whether utilized through simultaneous PET/MRI scanning or the co-registration of separately acquired PET and MRI data, present unique advantages, having complementary roles in lesional and non-lesional cases. Simultaneous FDG-PET/MRI provides precise co-registration of functional (PET) and structural (MR) imaging in a convenient one-stop-shop approach, which minimizes sedation time and reduces radiation exposure in children. Commercially available fusion software that allows retrospective co-registration of separately acquired PET and MRI images is a commonly used alternative. This review provides an overview and illustrative cases that highlight the role of combining 18F-FDG-PET and MRI imaging and shares the authors' decade-long experience utilizing simultaneous PET/MRI in the presurgical evaluation of pediatric epilepsy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The increasing usage of positron emission tomography/computed tomography (PET/CT) for detection and monitoring of malignancy has led to an increase in incidental detection of thyroid nodules. Nodules that demonstrate increased avidity for 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) have been shown to carry a high incidence of malignancy and warrant further investigation. At present, there has been limited research on the risk stratification of FDG-avid thyroid incidentalomas. Thus, this study aims to evaluate the efficacy of the ACR TIRADS classification in the risk stratification of such nodules., Methods: Data were collected retrospectively for FDG-avid thyroid incidentalomas over a 10-year period. Nodules were characterised using the TIRADS classification and, subsequently, underwent fine-needle aspirate cytology. Cytological findings were classified using the Bethesda reporting system. Non-diagnostic samples (Bethesda class I) were excluded. The remaining samples were divided into two groups: benign (Bethesda class II) or suspicious for malignancy/malignant (Bethesda class III or above)., Results: Thirty-six percent of low-risk nodules and 45% of high-risk nodules were malignant, respectively (P = 0.516). The sensitivity and specificity of TIRADS for detection of malignant nodules were 56% and 54%, respectively. There were no malignant TIRADS 1 or 2 nodules. The absence of any suspicious sonographic features had a 1.0 negative predictive value., Conclusions: FDG-avid nodules classified as TIRADS 1 or 2 or have no suspicious ultrasound features have a 0% incidence of malignancy and thus may not require further assessment with fine-needle aspirate cytology (FNA) when detected incidentally. FDG-avid nodules that are TIRADS 3 or above should undergo FNA regardless of size due to the high risk of malignancy and poor sensitivity of the TIRADS classification system., (© 2024 Royal Australian and New Zealand College of Radiologists.)

Abstract: Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Primary pediatric lung tumors are uncommon and have many overlapping clinical and imaging features. In contrast to adult lung tumors, these rare pediatric neoplasms have a relatively broad histologic spectrum. Informed by a single-institution 13-year retrospective record review, we present an overview of the most common primary pediatric lung neoplasms, with a focus on the role of positron emission tomography (PET), specifically 18 F-fluorodeoxyglucose (FDG) PET and 68 Ga-DOTATATE PET, in the management of primary pediatric lung tumors. In addition to characteristic conventional radiographic and cross-sectional imaging findings, knowledge of patient age, underlying cancer predisposition syndromes, and PET imaging features may help narrow the differential. While metastases from other primary malignancies remain the most commonly encountered pediatric lung malignancy, the examples presented in this pictorial essay highlight many of the important conventional radiologic and PET imaging features of primary pediatric lung malignancies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim was to investigate to what extent the quantification of myocardial blood flow (MBF) from dynamic 13 N-NH 3 positron emission tomography (PET) images is affected by time frame schemes, time-of-flight (ToF), reconstruction algorithms, blood pool volume of interest (VOI) locations and compartment models in patients with suspected chronic coronary syndrome., Methods: A standard MBF value was determined from 25 patients' rest/stress 13 N-NH 3 PET/CT images reconstructed with ordered subset expectation maximization (OSEM), 5 s time frame for the first frames without ToF, subsequently analyzed using a basal VOI and the deGrado compartment model. MBFs calculated using 2 or 10 s for the first frames, ToF, block-sequential regularized expectation maximization (BSREM), apical or large VOI, Hutchins or Krivokapich compartment models were compared to MBF standard in Bland-Altman plots (bias ± SD)., Results: Good agreement in global rest/stress MBF (mL/min/g) was found when changing the time frame scheme or reconstruction algorithm (MBF standard vs. MBF 2s : -0.02 ± 0.06; MBF 10s : 0.01 ± 0.07; MBF BSREM : 0.01 ± 0.07), while a lower level of agreement was found when altering the other factors (MBF standard vs. MBF ToF : -0.07 ± 0.10; MBF apical VOI : -0.27 ± 0.25; MBF large VOI : -0.11 ± 0.10; MBF Hutchins : -0.08 ± 0.10; MBF Krivokapich : -0.47 ± 0.50)., Conclusions: Quantification of MBF from 13 N-NH 3 PET images is more affected by choice of compartment models, ToF and blood pool VOIs than by different time frame schemes and reconstruction algorithms., (© 2023 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Pancreatic cancers are the third leading cause of cancer-related death in the USA and outcomes remain poor despite improvements in imaging and treatment paradigms. Currently, computed tomography (CT) and magnetic resonance imaging (MRI) are frequently utilized for staging and restaging of these malignancies, but positron emission tomography (PET)/CT can play a role in troubleshooting and improve whole-body staging. PET/MRI is a novel imaging modality that allows for simultaneous acquisition of PET and MRI images, leading to improved image quality and potential increased sensitivity. Early studies suggest that PET/MRI may play a larger role in pancreatic cancer imaging in future. This manuscript will briefly discuss current imaging approaches to pancreatic cancer and outline existing evidence and published data supporting the use of PET/MRI for pancreatic cancers., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Amyloid positron emission tomography (PET) with F-18 florbetaben (FBB), F-18 flutemetamol (FMM), and F-18 florapronol (FPN) is being used clinically for the evaluation of dementia. These radiopharmaceuticals are commonly used to evaluate the accumulation of beta-amyloid plaques in the brain, but there are structural differences between them. We investigated whether there are any differences in the imaging characteristics., Methods: A total of 605 subjects were enrolled retrospectively in this study, including healthy subjects (HS) and patients with mild cognitive impairment or Alzheimer's disease. Participants underwent amyloid PET imaging using one of the three radiopharmaceuticals. The PET images were analyzed visually and semi-quantitatively using a standardized uptake value ratio (SUVR). In addition, we calculated and compared the cut-off SUVR of the representative regions for each radiopharmaceutical that can distinguish between positive and negative scans., Results: In the negative images of the HS group, the contrast between the white matter and the gray matter was high in the FMM PET images, while striatal uptake was relatively higher in the FPN PET images. The SUVR showed significant differences across the radiopharmaceuticals in all areas except the temporal lobe, but the range of differences was relatively small. Accuracy levels for the global cut-off SUVR to discriminate between positive and negative images were highest in FMM PET, with a value of 0.989. FBB PET also showed a high value of 0.978, while FPN PET showed a relatively low value of 0.901., Conclusions: Negative amyloid PET images using the three radiopharmaceuticals showed visually and quantitatively similar imaging characteristics except in the striatum. Binary classification using the cut-off of the global cortex showed high accuracy overall, although there were some differences between the three PET images., (© 2023. The Author(s).)

Abstract: Extravasation during radiopharmaceutical injection may occur with a frequency of more than 10%. In these cases, radioactivity remains within tissue and deposits unintended radiation dose. Characterization of extravasations is a necessary step in accurate dosimetry, but a lack of free and publicly available tools hampers routine standardized analysis. Our objective was to improve existing extravasation characterization and dosimetry methods and to create and validate tools to facilitate standardized practical dosimetric analysis in clinical settings. Using Monte Carlo simulations, we calculated dosimetric values for sixteen nuclear medicine isotopes: 11 C, 64 Cu, 18 F, 67 Ga, 68 Ga, 123 I, 131 I, 111 In, 177 Lu, 13 N, 15 O, 82 Rb, 153 Sm, 89 Sr, 99m Tc, and 90 Y. We validated our simulation results against five logical alternative dose assessment methods. We then created three new characterization tools: a worksheet, a spreadsheet, and a web application. We assessed each tool by recalculating extravasation dosimetry results found in the literature and used each of the tools for patient cases to show clinical practicality. Average variation between our simulation results and alternative methods was 3.1%. Recalculation of published dosimetry results indicated an average error of 7.9%. Time required to use each characterization tool ranged from 1 to 5 min, and agreement between the three tools was favorable. We improved upon existing methods by creating new tools for characterization and dosimetry of radiopharmaceutical extravasation. These free and publicly available tools will enable standardized routine clinical analysis and benefit patient care, clinical follow-up, documentation, and event reporting., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

An editorial is presented which argues on complementary value of preclinical and clinical radiobiology research projects to rationalize the therapeutic use of radiopharmaceuticals. It presents the views on relevant preclinical models for radiobiology, recommendations on dosimetry in preclinical models and dose–effect relationship and quantitative radiobiological models.

Prostate-specific membrane antigen (PSMA) is a glycosylated type-II transmembrane protein expressed in prostatic tissue and significantly overexpressed in several prostate cancer cells. Despite its name, PSMA has also been reported to be overexpressed in endothelial cells of benign and malignant non-prostate disease. So its clinical use was extended to detection, staging, and therapy of various tumor types. Recently small molecules targeting PSMA have been developed as imaging probes for diagnosis of several malignancies. Preliminary studies are emerging improved diagnostic sensitivity and specificity of PSMA imaging, leading to a change in patient management. In this review, we evaluated the first preclinical and clinical studies on PSMA ligands resulting future perspectives radiolabeled PSMA in staging and molecular characterization, based on histopathologic examinations of PSMA expression., (© 2021 John Wiley & Sons Ltd.)

Positron emission tomography (PET) is a quantitative imaging technique that uses molecules labeled with positron-emitting radionuclides to visualize and measure biochemical processes in the tissues of living subjects. In recent years, different PET tracers have been evaluated for their ability to characterize the atherosclerotic process in order to study the activity of the disease. Here, we describe detailed PET methods for preclinical studies of atherosclerosis and summarize the key methodological aspects of PET imaging in clinical studies of atherosclerosis., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite growing interest in coronary microvascular disease (CMVD), there is a dearth of mechanistic understanding. Mouse models offer opportunities to understand molecular processes in CMVD. We have sought to develop quantitative mouse imaging to assess coronary microvascular function., Methods: We used 99m Tc-sestamibi to measure myocardial blood flow in mice with MILabs U-SPECT + system. We determined recovery and crosstalk coefficients, the influx rate constant from blood to myocardium (K1), and, using microsphere perfusion, constraints on the extraction fraction curve. We used 99m Tc and stannous pyrophosphate for red blood cell imaging to measure intramyocardial blood volume (IMBV) as an alternate measure of microvascular function., Results: The recovery coefficients for myocardial tissue (R T ) and left ventricular arterial blood (R A ) were 0.81 ± 0.16 and 1.07 ± 0.12, respectively. The assumption R T  = 1 - FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measured K1 of 0.57 ± 0.08 min -1 . Constraints on the extraction fraction curve for 99m Tc-sestamibi in mice for best-fit Renkin-Crone parameters were α = 0.99 and β = 0.39. Additionally, we found that wild-type mice increase their IMBV by 22.9 ± 3.3% under hyperemic conditions., Conclusions: We have developed a framework for measuring K1 and change in IMBV in mice, demonstrating non-invasive µSPECT-based quantitative imaging of mouse microvascular function., (© 2020. American Society of Nuclear Cardiology.)

The use of various types of radioactive drugs has increased the effectiveness of nuclear medicine. Technetium-99m (99mTc) radiopharmaceuticals are in widespread use owing to the availability and affordability of 99Mo/99mTc generators and the variety of kits for formulating the desired products. Together, they provide an array of specific tools for diagnosing a large number of diseases affecting the Heart, Kidney and major organs of the body such as the bones, brain, liver, parathyroid, and thyroid. Nuclear medicine requires high quality radiopharmaceuticals and kits that are safe for administration and efficacious for a given application. Since radiopharmaceuticals are intended for human use, it is imperative that they undergo quality control measure. This paper presents various parameters affecting labeling efficiency of radiopharmaceuticals and describes the procedures of preparing from four selected kits. Details of the ingredients are also included. The procedures described here can be used to develop manuals and standard operating procedures in Egypt. This study is expected to serve as a guide to radiopharmaceutical manufacturing centers of such kits. Four kits namely: MIBI, DTPA, MDP, and DMSA are used. Paper Chromatography was involved to disparate the polar and non-polar part of the kit-solution. Quality control testing assures purity, integrity, potency, product identity, biological safety and efficacy of radiopharmaceuticals. The success of diagnostic radiopharmaceutical has been reflected in the quality of images of diseased site. [ABSTRACT FROM AUTHOR]

Background: Texture analysis has been increasingly used in the field of positron emission tomography (PET)/computed tomography (CT) imaging with Fluorine-18 fluorodeoxyglucose (18F-FDG), aiming at assessing tumor heterogeneity. The purpose of the present study is to examine the feasibility of performing texture analysis in carotid arteries, investigate the value of textural features as predictors of potential plaque vulnerability using as reference standards histological and immunohistochemical data and compare their performance with conventional uptake measurements., Methods: 67 different 18F-FDG PET-based textural features were extracted from carotid images of 21 patients with high-grade carotid stenosis undergoing endarterectomy. To identify the more reliable predictors, univariate logistic regression analysis was performed. The accuracy was satisfactory in case of an Area Under the Receiver Operating Characteristic (ROC) curve (AUC) ≥ 0.80., Results: First measure of information correlation (AUC = 0.87, P < 0.001), large zone low gray level emphasis (AUC = 0.87, P < 0.001), and normalized run length non-uniformity (AUC = 0.84, P < 0.001) were the most optimal textural features for identifying characteristics of plaque vulnerability based on histological analysis. Addition of textural features to target-to-background ratio (TBR) (AUC = 0.74, P = 0.031) resulted in an AUC = 0.92 (P < 0.001), however, this did not reach statistical significance (P diff  = 0.09). Intensity histogram standard deviation (AUC = 0.87, P < 0.001) and joint variance (AUC = 0.81, P = 0.001) were the most efficient features for signal differential in relation to immunohistochemical findings and provided incremental value compared to TBR (P diff  = 0.02)., Conclusion: Texture analysis can be applied in 18F-FDG PET carotid imaging providing valuable information for plaque characterization., (© 2019. American Society of Nuclear Cardiology.)

Background: The cardiovascular committee of the European Association of Nuclear Medicine (EANM) recently published recommendations on imaging conditions to be observed during 18 F-FDG PET imaging of vascular inflammation. This study aimed to evaluate the impact of applying these optimized imaging conditions on PET quantification of arterial 18 F-FDG uptake., Methods and Results: Fifty-seven patients were prospectively recruited to undergo an early 18 F-FDG PET/CT imaging at 60 minutes and repeat delayed imaging at ≥ 120 minutes post tracer injection. Routine oncologic 18 F-FDG PET protocol was observed for early imaging, while delayed imaging parameters were optimized for vascular inflammation imaging as recommended by the EANM. Aortic SUVmax of the ascending aorta and SUVmean from the lumen of the superior vena cava (SVC SUVmean) were obtained on early and delayed imaging. Target-to-background ratio (TBR) was obtained for the early and delayed imaging. Aortic SUVmax increased by a mean of 70%, while SVC SUVmean decreased by a mean of 52% between early and delayed imaging (P < 0.001). TBR increased by 122% following delayed imaging. TBR increased, while SVC SUVmean declined across all time-points from 120 to > 180 minutes. Aortic SUVmax significantly increased at imaging time-points between 120 and 180 minutes. No significant improvement in aortic SUVmax was seen at imaging time-points beyond 180 minutes., Conclusions: 18 F-FDG PET imaging conditions optimized for vascular inflammation imaging lead to an improved quantification through an increase in the quantified vascular tracer uptake and decrease in blood-pool background activity., (© 2019. American Society of Nuclear Cardiology.)

About 35% reduction in cancer deaths among patients having solid tumors is related to using aspirin, which encouraged us to develop a new specific tumor diagnostic radiopharmaceutical agent. This can be done by direct labeling of aspirin with technetium-99m using stannous chloride as a reductant at pH 9. At this pH, aspirin is saponificated to salicylate ions. Salicylate binds to pertechenetate to form 99mTc salicylate complex. The radiochemical yield (RCY, %) of 99mTc-salicylate complex obtained from aspirin was determined using paper chromatography, electrophoresis, and HPLC and was found to reach 90.2%. The 99mTc salicylate complex obtained from aspirin was stable for up to 5 h. The tumor uptake of the 99mTc salicylate complex obtained from aspirin was determined by ex-vivo study in tumor-bearing mice. This study showed that 99mTc salicylate complex was concentrated in tumor sites (ascites or solid), allowing tumor radioimaging. High target/non-target (tumor muscles/normal muscles) uptake ratio shows that 99mTc salicylate complex can be utilized for early detection of solid tumors. Molecular modeling and docking study conofirm the possibility of using the radiolabeled 99mTc salicylate complex for specific cancer imaging in binding with epidermal growth factor receptors (EGFR). [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that cardiac involvement in patients with granulomatosis with polyangiitis (GPA) occurs more frequently than previously reported. Multimodality cardiac imaging is gaining attention in the diagnosis, prognostication, and follow-up of such patients; however, the data remain scarce., Results: 2D-TTE was useful for initial screening; while both cardiac magnetic resonance imaging and 18 F-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 FDG-PET/CT) metabolic imaging with rubidium-82 PET perfusion imaging were useful for characterization of myocardial disease. 18 FDG-PET/CT was very useful for the follow-up of cardiac disease activity following treatment., Conclusion: 18 FDG-PET/CT is sensitive for the detection of cardiac involvement by GPA and is useful for the tissue characterization and follow-up of disease activity following treatment.

Purpose: The folate receptor (FR) is frequently overexpressed in a variety of tumor types and, hence, an interesting target for radionuclide therapy. The aim of this study was to evaluate a new class of albumin-binding radioconjugates comprising 5-methyltetrahydrofolate (5-MTHF) as a targeting agent and to compare their properties with those of the previously established folic acid-based [ 177 Lu]Lu-OxFol-1., Methods: [ 177 Lu]Lu-6R-RedFol-1 and [ 177 Lu]Lu-6S-RedFol-1 were investigated in vitro using FR-positive KB tumor cells. Biodistribution studies were performed in KB tumor-bearing mice, and the areas under the curve (AUC 0 → 120h ) were determined for the uptake in tumors and kidneys. [ 177 Lu]Lu-6R-RedFol-1 was compared with [ 177 Lu]Lu-OxFol-1 in a therapy study over 8 weeks using KB tumor-bearing mice., Results: Both radioconjugates demonstrated similar in vitro properties as [ 177 Lu]Lu-OxFol-1; however, the tumor uptake of [ 177 Lu]Lu-6R-RedFol-1 and [ 177 Lu]Lu-6S-RedFol-1 was significantly increased in comparison with [ 177 Lu]Lu-OxFol-1. In the case of [ 177 Lu]Lu-6S-RedFol-1, also the kidney uptake was increased; however, renal retention of [ 177 Lu]Lu-6R-RedFol-1 was similar to that of [ 177 Lu]Lu-OxFol-1. This led to an almost 4-fold increased tumor-to-kidney AUC 0 → 120h ratio of [ 177 Lu]Lu-6R-RedFol-1 as compared with [ 177 Lu]Lu-6S-RedFol-1 and [ 177 Lu]Lu-OxFol-1. At equal activity, the therapeutic effect of [ 177 Lu]Lu-6R-RedFol-1 was better than that of [ 177 Lu]Lu-OxFol-1, reflected by a slower tumor growth and, consequently, an increased median survival time (49 days vs. 34 days)., Conclusion: This study demonstrated the promising potential of 5-MTHF-based radioconjugates for FR-targeting. Application of [ 177 Lu]Lu-6R-RedFol-1 resulted in unprecedentedly high tumor-to-kidney ratios and, as a consequence, a superior therapeutic effect as compared with [ 177 Lu]Lu-OxFol-1. These findings, together with the absence of early side effects, make [ 177 Lu]Lu-6R-RedFol-1 attractive in view of a future clinical translation.

Aims: 68 Ga-Prostate-specific membrane antigen (PSMA) PET/CT is widely used in patients with biochemical recurrence (BCR) after radical prostatectomy. We collected data about patients staged with PSMA PET/CT after BCR (PSA < 1 ng/ml) in four different institutes. Impact of baseline features (Gleason score, risk classification, PSA at recurrence, PSA doubling time and time to recurrence) was explored to understand predictive factors of (PSMA) PET/CT positivity. Impact of restaging on following treatment approaches was reported., Results: 92 patients were included. PSMA PET/CT detection rate was 56.5% and low-volume disease (≤ 3 non-visceral lesions) was detected in 52.2% of patients. After positive scan, 13.5% of patients still lies on observation, ADT alone was administered in 30.8% of cases, Stereotactic body RT (SBRT) alone was delivered to 44.2% of patients and 11.5% of patients underwent concomitant SBRT and ADT. Seven patients underwent conventional salvage prostate bed RT. Chi-squared test showed a higher rate of positive PSMA PET/CT for patients with Gleason score > 7 (p = 0.004) and TTR < 29.5 months (p = 0.003)., Conclusions: PSMA PET/CT showed a high detection rate. This influenced clinical management in a significant percentage of patients, allowing treatment tailoring on the basis of imaging.

Radiopharmaceuticals means radionuclide preparations or labeled compounds for clinical diagnosis or therapeutic use. Radiochemical purity is one of the important judgment indexes to measure the quality of radiopharmaceuticals, which directly affects the clinical effect, it is very important to accurately determine and strictly control the radiochemical purity. In this paper, by querying and analyzing Chinese Pharmacopoeia 2020, European Pharmacopoeia 10.2, US Pharmacopoeia 43-NF38, and the related literature, making a analysis and summary on the characteristics, separation principle and application of commonly used radiochemical purity determination methods, including thin-layer chromatography (TLC), paper chromatography (PC), electrophoresis (EP) and high performance liquid chromatography (HPLC), which would help to establish a more scientific and reasonable standard of radiopharmaceuticals quality standards and to provide technical reference.

The purposes of this study were as follows: (1) to radiolabel ibandronic acid (IBA, a third‐generation bisphosphonate) with 177Lu, investigating optimal labeling conditions, and (2) to analyze biodistribution and imaging properties of intravenous 177Lu‐ibandronate (177Lu‐IBA) administered in animals. 177Lu‐labeled methylene diphosphonate (177Lu‐MDP) served as a comparator agent. Differing proportions of IBA solution and 177LuCl3 solution were combined to determine an optimal ratio for radiolabeling purposes, varying pH, temperature, and time to establish ideal reactivity conditions. Radiochemical purity of the labeled compounds was then assessed by paper chromatography. In vitro and in vivo stabilities were also measured at specific time intervals. In Kunming mice, biodistributions of 177Lu‐IBA and 177Lu‐MDP and respective agent activities in various organs were monitored by gamma counter, and we performed single photon computed tomography/computed tomography (SPECT/CT) imaging of 177Lu‐IBA in normal New Zealand White rabbits. Radiolabeling yields for 177Lu‐IBA proved to be >97% within 30 minutes at 90°C, and its radiochemical purity ensured stability in vitro and in vivo. Furthermore, we found that 177Lu‐IBA is readily soluble in water, showing higher skeletal uptake than 177Lu‐MDP but lower uptake by liver and spleen. The image quality of 177Lu‐IBA was so clear that even after 6 days, analysis was still feasible. To develop a new efficient and safe bone‐seeking radiopharmaceutical, 177Lu‐ibandronate, for bone pain palliation, which could be used for the purposes of both treatment and monitoring of the patient's condition. [ABSTRACT FROM AUTHOR]

A previously published paper in the official journal of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) concluded that the artificial intelligence chatbot ChatGPT may offer an adequate substitute for nuclear medicine staff informational counseling to patients in an investigated setting of 18F-FDG PET/CT. To ensure consistency with the previous paper, the author and a team of experts followed a similar methodology and evaluated whether ChatGPT could adequately offer a substitute for nuclear medicine staff informational counseling to patients regarding radiopharmaceutical extravasations. We asked ChatGPT fifteen questions regarding radiopharmaceutical extravasations. Each question or prompt was queried three times. Using the same evaluation criteria as the previously published paper, the ChatGPT responses were evaluated by two nuclear medicine trained physicians and one nuclear medicine physicist for appropriateness and helpfulness. These evaluators found ChatGPT responses to be either highly appropriate or quite appropriate in 100% of questions and very helpful or quite helpful in 93% of questions. The interobserver agreement among the evaluators, assessed using the Intraclass Correlation Coefficient (ICC), was found to be 0.72, indicating good overall agreement. The evaluators also rated the inconsistency across the three ChatGPT responses for each question and found irrelevant or minor inconsistencies in 87% of questions and some differences relevant to main content in the other 13% of the questions. One physician evaluated the quality of the references listed by ChatGPT as the source material it used in generating its responses. The reference check revealed no AI hallucinations. The evaluator concluded that ChatGPT used fully validated references (appropriate, identifiable, and accessible) to generate responses for eleven of the fifteen questions and used generally available medical and ethical guidelines to generate responses for four questions. Based on these results we concluded that ChatGPT may be a reliable resource for patients interested in radiopharmaceutical extravasations. However, these validated and verified ChatGPT responses differed significantly from official positions and public comments regarding radiopharmaceutical extravasations made by the SNMMI and nuclear medicine staff. Since patients are increasingly relying on the internet for information about their medical procedures, the differences need to be addressed. [ABSTRACT FROM AUTHOR]

This is a position paper of the Radiopharmacy Committee of the EANM (European Association of Nuclear Medicine) addressing toxicology studies for application of new diagnostic and therapeutic radiopharmaceuticals (RP) that are not approved (i.e., not having a marketing authorization or a monograph in the European Pharmacopoeia), excluding endogenous and ubiquitous substances in humans. This paper discusses the requirements for clinical trials with radiopharmaceuticals for clinical research applications, not necessarily intended to aim at a marketing authorization. If marketing authorization is intended, scientific advice of the competent authorities is mandatory and cannot be replaced by this position paper. The position paper reflects the view of the Radiopharmacy Committee of the EANM and can be used as a basis for discussions with the responsible authorities. [ABSTRACT FROM AUTHOR]

The report of an imaging procedure is a critical component of an examination, being the final and often the only communication from the interpreting physician to the referring or treating physician. Very limited evidence and few recommendations or guidelines on reporting imaging studies are available; therefore, an European position statement on how to report nuclear cardiology might be useful. The current paper combines the limited existing evidence with expert consensus, previously published recommendations as well as current clinical practices. For all the applications discussed in this paper (myocardial perfusion, viability, innervation, and function as acquired by single photon emission computed tomography and positron emission tomography or hybrid imaging), headings cover laboratory and patient demographics, clinical indication, tracer administration and image acquisition, findings, and conclusion of the report. The statement also discusses recommended terminology in nuclear cardiology, image display, and preliminary reports. It is hoped that this statement may lead to more attention to create well-written and standardized nuclear cardiology reports and eventually lead to improved clinical outcome. [ABSTRACT FROM AUTHOR]

The materials, techniques, and instruments for the detection and quantification of radiolabeled compounds by planar radiochromatography are described. Included is sample preparation; separations on Instant Thin Layer Chromatography sheets, thin layer plates, and chromatography papers; and detection and quantification by film autoradiography, liquid scintillation counting, storage phosphor imaging, and in situ radioactivity scanning. These methods are widely applied in radiopharmaceutical purity determination, metabolism studies, and many other types of chemical, biochemical, and biological investigations. [ABSTRACT FROM AUTHOR]