Nuclear medicine and pediatric nephro-urology: a long-lasting successful partnership.

Congenital anomalies of the kidney and urinary tract, as well as urinary infections, are very frequent in children. After the clinical and laboratory evaluation, the first imaging procedure to be done is a renal and bladder ultrasound, but afterwards, a main contribution comes from nuclear medicine. Through minimally invasive and sedation-free procedures, nuclear medicine allows the evaluation of the functional anatomy of the urinary tract, and the quantification of renal function and drainage. If pediatric dosage cards provided by scientific societies are used, radiation exposure can also be low. In the pediatric conditions previously mentioned, nuclear medicine is used both for initial diagnosis and follow-up, mostly in cases of suspicion of ureteropelvic or ureterovesical junction syndromes, as well as vesicoureteral reflux or renal scars of febrile infectious episodes. Pediatric nephro-urology constitutes a significant workload of pediatric nuclear medicine departments. The following paragraphs are a revision of the renal radiopharmaceuticals, as well as the nuclear nephro-urology procedures - dynamic and static renal scintigraphy, and direct and indirect radionuclide cystography. A summary of the techniques, main indications, interpretation criteria and pitfalls will be provided. Some future directions for the field are also pointed out, among which the most relevant is the need for nuclear medicine professionals to use standardized protocols and integrate multidisciplinary teams with other pediatric and adult health professionals that manage these life-long pediatric pathologies, which are recognized as an important cause of adult chronic kidney disease.

EANM guidance document: dosimetry for first-in-human studies and early phase clinical trials.

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.

A Brief History of Nuclear Medicine Imaging of Infection.

For nearly 50 years, nuclear medicine has played an important role in the diagnosis of infection. Gallium citrate Ga 67 was one of the first, if not the first, radionuclide used for this purpose. Unfavorable imaging characteristics, a lack of specificity, and the long interval (2-3 days) between administration and imaging spurred the search for alternatives. At the present time, gallium 67 citrate is used primarily for differentiating acute tubular necrosis from interstitial nephritis and as an alternative for indications including sarcoid, spondylodiscitis, and fever of unknown origin, when 18F-fluorodeoxyglucose (18F-FDG) is not available. The approval, in the mid-1980s, of techniques for in vitro labeling of leukocytes with indium-111 and technetium-99m that subsequently migrate to foci of infection was a significant advance in nuclear medicine imaging of infection and labeled leukocyte imaging still plays an important role in imaging of infection. There are significant disadvantages to in vitro labeled leukocyte imaging. Unfortunately, efforts devoted to developing in vivo leukocyte labeling methods have met with only limited success. Over the past 20 years 18F-FDG has established itself as a valuable imaging agent for musculoskeletal and cardiovascular infections, as well as sarcoidosis and fever of unknown origin. As useful as these agents are, their uptake is based on the host response to infection, not infection itself. Previous attempts at developing infection-specific agents, including radiolabeled antibiotics and vitamins, were limited by poor results and/or lack of availability, so investigators continue to focus on developing infection-specific nuclear medicine imaging agents.

Synthesis of 177Lu-Labeled, Somatostatin-2 Receptor-Targeted Metalla-Assemblies: Challenges in the Design of Supramolecular Radiotherapeutics.

Self-assembled supramolecular coordination complexes (SCCs) hold promise for biomedical applications in cancer therapy, although their potential in the field of nuclear medicine is still substantially unexplored. Therefore, in this study an exo-functionalized cationic [Pd2L2]4+ metallacycle (L = 3,5-bis(3-ethynylpyridine)phenyl), targeted to the somatostatin-2 receptor (sst2R) and featuring the DOTA chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) in order to bind the ß-- and γ-emitter lutetium-177, was synthesized by self-assembly following ligand synthesis via standard solid-phase peptide synthesis (SPPS). This metallacycle was then characterized by reverse-phase high-performance liquid chromatography (RP-HPLC), electrospray ionization mass spectrometry (ESI-MS), and 1H and 1H-DOSY NMR (DOSY = diffusion-ordered spectroscopy). A procedure for the radiolabeling of the metallacycle with 177Lu was also optimized. The resulting [nat/177Lu]Lu-DOTA-metallacycle, termed [nat/177Lu]Lu-Cy, was evaluated concerning its stability and in vitro properties. The compound was more lipophilic compared to the reference [177Lu]Lu-DOTA-TATE (logPOct/H2O = -0.85 ± 0.10 versus -3.67 ± 0.04, respectively). While [natLu]Lu-Cy revealed low stability in a DMEM/F12 GlutaMax medium, it demonstrated good stability in other aqueous media as well as in DMSO. A high sst2R binding affinity (expressed as IC50) was determined in CHOsst2 cells (Chinese hamster ovary cells that were stably transfected with human sst2R). Moreover, the metallacycle exhibited high human serum albumin binding, as assessed by high-performance affinity chromatography (HPAC), and moderate stability in human serum compared to [177Lu]Lu-DOTA-TATE (TATE = (Tyr3)-octreotate). In order to improve stability, a heteroleptic approach was used to develop a less sterically hindered cage-like SCC that is potentially endowed with host-guest chemistry capability, which has been preliminarily characterized by RP-HPLC and ESI-MS. Overall, our initial results encourage future studies on sst2R-directed SCCs and have led to new insights into the chemistry of ss2R-directed SCCs for radiopharmaceutical applications.

What Is New in Risk Assessment in Nuclear Cardiology?

Nuclear cardiology techniques allow in-depth evaluation of cardiac patients. A body of literature has established the use of nuclear cardiology. The results obtained with traditional cameras have been reinforced by those obtained with a series of innovations that have revolutionized the field of nuclear cardiology. This article highlights the role of nuclear cardiology in the risk assessment of patients with cardiac disease and sheds light on advancements of nuclear imaging techniques in the cardiovascular field. Patient risk stratification has a key role in modern precision medicine. Nuclear cardiac imaging techniques may quantitatively investigate major disease mechanisms of different cardiac pathologies.

2022 SNMMI Highlights Lecture: General Nuclear Medicine.

The Highlights Lectures at the closing sessions of SNMMI Annual Meetings were originated and presented for more than 30 y by Henry N. Wagner, Jr., MD. Beginning in 2010, the duties of summarizing selected significant presentations at the meeting were divided annually among 4 distinguished nuclear and molecular medicine subject matter experts. The 2022 Highlights Lectures were delivered on June 14 at the SNMMI Annual Meeting in Vancouver, Canada. This month we feature the lecture by Andrei Iagaru, MD, Professor of Radiology-Nuclear Medicine at Stanford University School of Medicine (CA) and Chief of the Division of Nuclear Medicine and Molecular Imaging at Stanford HealthCare, who spoke on general nuclear medicine highlights from the meeting. Note that in the following presentation summary, numerals in brackets represent abstract numbers as published in The Journal of Nuclear Medicine (2022;63[suppl 2]).

Hot spot imaging in cardiovascular diseases: an information statement from SNMMI, ASNC, and EANM.

This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.

The potential of a medium-cost long axial FOV PET system for nuclear medicine departments.

PURPOSE: Total body positron emission tomography (TB-PET) has recently been introduced in nuclear medicine departments. There is a large interest in these systems, but for many centers, the high acquisition cost makes it very difficult to justify their current operational budget. Here, we propose medium-cost long axial FOV scanners as an alternative. METHODS: Several medium-cost long axial FOV designs are described with their advantages and drawbacks. We describe their potential for higher throughput, more cost-effective scanning, a larger group of indications, and novel research opportunities. The wider spread of TB-PET can also lead to the fast introduction of new tracers (at a low dose), new methodologies, and optimized workflows. CONCLUSIONS: A medium-cost TB-PET would be positioned between the current standard PET-CT and the full TB-PET systems in investment but recapitulate most advantages of full TB-PET. These systems could be more easily justified financially in a standard academic or large private nuclear medicine department and still have ample research options.

Joint EANM/SNMMI guideline on radiomics in nuclear medicine : Jointly supported by the EANM Physics Committee and the SNMMI Physics, Instrumentation and Data Sciences Council.

PURPOSE: The purpose of this guideline is to provide comprehensive information on best practices for robust radiomics analyses for both hand-crafted and deep learning-based approaches. METHODS: In a cooperative effort between the EANM and SNMMI, we agreed upon current best practices and recommendations for relevant aspects of radiomics analyses, including study design, quality assurance, data collection, impact of acquisition and reconstruction, detection and segmentation, feature standardization and implementation, as well as appropriate modelling schemes, model evaluation, and interpretation. We also offer an outlook for future perspectives. CONCLUSION: Radiomics is a very quickly evolving field of research. The present guideline focused on established findings as well as recommendations based on the state of the art. Though this guideline recognizes both hand-crafted and deep learning-based radiomics approaches, it primarily focuses on the former as this field is more mature. This guideline will be updated once more studies and results have contributed to improved consensus regarding the application of deep learning methods for radiomics. Although methodological recommendations in the present document are valid for most medical image modalities, we focus here on nuclear medicine, and specific recommendations when necessary are made for PET/CT, PET/MR, and quantitative SPECT.

EANM practice guideline for quantitative SPECT-CT.

PURPOSE: Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases. METHODS: These practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT. The guidelines have also been reviewed and approved by all EANM committees and have been endorsed by the European Association of Nuclear Medicine. CONCLUSION: The present practice guidelines will help practitioners, scientists and researchers perform high-quality quantitative SPECT-CT and will provide a framework for the continuing development of quantitative SPECT-CT as an established modality.

Aportaciones de la medicina nuclear en la enfermedad musculoesquelética tumoral maligna en niños / Contributions of nuclear medicine to malignant musculoskeletal tumor disease in children

Un diagnóstico de cáncer es perturbador a cualquier edad, pero especialmente cuando el paciente es un niño. Solo se puede diagnosticar lo que se sospecha, solo se sospecha lo que se conoce o, al menos, se conoce su existencia, pero los tumores musculoesqueléticos son infrecuentes y, por tanto, muy difíciles de diagnosticar o tratar. Probablemente por su infrecuencia, por la complejidad de las imágenes radiológicas, por la apariencia histopatológica, así como por las serias consecuencias debido a biopsias y tratamientos inadecuados, la patología tumoral musculoesquelética necesita un manejo clínico que debe ser llevado a cabo por un grupo de especialistas con formación específica, que permita un adecuado diagnóstico, la introducción de terapias adyuvantes, así como un tratamiento quirúrgico, haciéndose hoy imprescindible un tratamiento multidisciplinar. Los estudios de imagen proporcionan información esencial sobre la naturaleza de cada lesión, su tamaño, su localización anatómica, el efecto sobre el hueso o los tejidos blandos circundantes y la afectación de las articulaciones adyacentes y las estructuras neurovasculares. En este artículo los autores analizan los avances de las técnicas de medicina nuclear (gammagrafías, PET/TC y SPECT/TC) y su utilidad en la estadificación de tumores musculoesqueléticos malignos pediátricos, así como en la valoración de la respuesta, el seguimiento y el diagnóstico de recidiva (AU)

A diagnosis of cancer is frightening at any age, but especially when the patient is a child. Only what is suspected can be diagnosed, only what is known or at least known to exist is suspected, but musculoskeletal tumors are infrequent and therefore very difficult to diagnose or treat. Probably due to their infrequency, the complexity of the radiological images, histopathological appearance, as well as the serious consequences due to inadequate biopsies and treatments, musculoskeletal tumor pathology requires clinical management that must be carried out by a group of specialists with specific training, allowing an adequate diagnosis, introduction of adjuvant therapies, as well as surgical treatment, making multidisciplinary treatment essential today. Imaging studies provide essential information on the nature of each lesion, its size, its anatomical location, the effect on the surrounding bone or soft tissues and the involvement of adjacent joints and neurovascular structures. In this article the authors will discuss the advances in nuclear medicine techniques (scintigraphy, SPECT/CT and PET/CT) and their usefulness in the staging of pediatric malignant musculoskeletal tumors, as well as in the assessment of response, follow-up, and diagnosis of recurrence (AU)

Nuclear medicine imaging methods as novel tools in the assessment of pulmonary drug disposition.

INTRODUCTION: Drugs for the treatment of respiratory diseases are commonly administered by oral inhalation. Yet surprisingly little is known about the pulmonary pharmacokinetics of inhaled molecules. Nuclear medicine imaging techniques (i.e. planar gamma scintigraphy, single-photon emission computed tomography [SPECT] and positron emission tomography [PET]) enable the noninvasive dynamic measurement of the lung concentrations of radiolabeled drugs or drug formulations. This review discusses the potential of nuclear medicine imaging techniques in inhalation biopharmaceutical research. AREAS COVERED: (i) Planar gamma scintigraphy studies with radiolabeled inhalation formulations to assess initial pulmonary drug deposition; (ii) imaging studies with radiolabeled drugs to assess their intrapulmonary pharmacokinetics; (iii) receptor occupancy studies to quantify the pharmacodynamic effect of inhaled drugs. EXPERT OPINION: Imaging techniques hold potential to bridge the knowledge gap between animal models and humans with respect to the pulmonary disposition of inhaled drugs. However, beyond the mere assessment of the initial lung deposition of inhaled formulations with planar gamma scintigraphy, imaging techniques have rarely been employed in pulmonary drug development. This may be related to several technical challenges encountered with such studies. Considering the wealth of information that can be obtained with imaging studies their use in inhalation biopharmaceutics should be further investigated.