Joint EANM-SNMMI guideline on the role of 2-[18F]FDG PET/CT in no special type breast cancer : (endorsed by the ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA).

INTRODUCTION: There is much literature about the role of 2-[18F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject. PURPOSE: To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). METHODS: Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[18F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria. RESULTS: Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[18F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[18F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[18F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[18F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising. CONCLUSION: 2-[18F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.

Women's Health Update: Growing Role of PET for Patients with Breast Cancer.

Positron Emission Tomography (PET) has been growing in usage for patients with breast cancer, due to an increased number of FDA-approved PET radiotracers pertinent to patients with breast cancer as well as increased prospective evidence for the value of these agents. The leading PET radiotracer for patients with breast cancer is 18F-fluorodeoxyglucose (18F-FDG), which measures glucose metabolism. There is prospective evidence for the use of 18F-FDG PET in systemic staging of newly diagnosed locally advanced breast cancer (stages IIB-IIIC), monitoring breast cancer treatment response, and detecting breast cancer recurrence, particularly in no special type (NST) breast cancer. 16α-18F-fluoro-17ß-Fluoroestradiol (18F-FES) is a radiolabeled estrogen which evaluates estrogen receptor (ER) accessible for estrogen binding. There is prospective evidence supporting 18F-FES PET as a predictive biomarker for selecting patients with metastatic breast cancer for endocrine therapies. 18F-FES PET has also been shown to be valuable in the evaluation of ER status of lesions which are difficult to biopsy, for evaluation of ER status in lesions that are equivocal on other imaging modalities, and for selecting optimal dosage of novel ER-targeted systemic therapies in early clinical trials. Multiple investigators have suggested 18F-FES PET will have an increasing role for patients with invasive lobular breast cancer (ILC), which is less optimally evaluated by 18F-FDG PET. Sodium 18F-Fluoride (18F-NaF) evaluates bone turnover and has been effective in evaluation of malignancies which commonly metastasize to bone. In patients with metastatic breast cancer, 18F-NaF PET/CT has demonstrated superior sensitivity for osseous metastases than 99mTc-MDP or CT. In addition to these three FDA-approved PET radiotracers, there are multiple novel radiotracers currently in clinical trials with potential to further increase PET usage for patients with breast cancer.

Quarter-Century Transformation of Oncology: Positron Emission Tomography for Patients with Breast Cancer.

PET radiotracers have become indispensable in the care of patients with breast cancer. 18F-fluorodeoxyglucose has become the preferred method of many oncologists for systemic staging of breast cancer at initial diagnosis, detecting recurrent disease, and for measuring treatment response after therapy. 18F-Sodium Fluoride is valuable for detection of osseous metastases. 18F-fluoroestradiol is now FDA-approved with multiple appropriate clinical uses. There are multiple PET radiotracers in clinical trials, which may add utility of PET imaging for patients with breast cancer in the future. This article will describe the advances during the last quarter century in PET for patients with breast cancer.

Summary: SNMMI Procedure Standard/EANM Practice Guideline for Estrogen Receptor Imaging of Patients with Breast Cancer Using 16α-[18F]Fluoro-17ß-Estradiol PET.

The estrogen receptor (ER), a steroid hormone receptor important in female physiology, is a significant contributor to breast carcinogenesis and progression and, as such, is an important therapeutic target. Approximately 70% of breast cancers will express ER at presentation, and the determination of ER expression by tissue assay, usually by immunohistochemistry, is part of the standard of care for newly diagnosed breast cancer. ER expression is important in guiding the approach to treatment, especially with the increase in relevant systemic therapies. The ER-targeting imaging agent 16α-[18F]fluoro-17ß-estradiol ([18F]FES) is approved for clinical use by regulatory agencies in France and the United States. Multiple studies suggest the advantages of [18F]FES PET in assessing tumor ER expression, the ability of both qualitative and quantitative [18F]FES PET measures to predict response to ER-targeted therapy, and the ability of [18F]FES PET to clarify equivocal staging and restaging results in patients with ER-expressing cancers. [18F]FES PET/CT may also be helpful in staging invasive lobular breast cancer and low-grade ER-expressing invasive ductal cancers and, in some cases, may be a substitute for biopsy. The Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine in June 2023 released a procedure standard/practice guideline for [18F]FES PET ER imaging of patients with breast cancer. The goal of the standard/guideline is to assist physicians in recommending, performing, interpreting, and reporting the results of [18F]FES PET studies for patients with breast cancer and to provide clinicians with the best available evidence, inform them about areas where robust evidence is lacking, and help them deliver the best possible diagnostic efficacy and study quality for their patients. Also reviewed are standardized quality control, quality assurance, and imaging procedures for [18F]FES PET. The authors emphasize the importance of precision, accuracy, repeatability, and reproducibility for both clinical management of patients and for use of [18F]FES PET in multicenter trials. A standardized imaging procedure, in combination with already published appropriate-use criteria, will help promote the use of [18F]FES PET and enhance subsequent research. This brief summary article reviews the content of the joint standard/guideline, which is available in its entirety at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=6414&navItemNumbe=10790.

PET/CT in Patients with Breast Cancer Treated with Immunotherapy.

Significant advances in breast cancer (BC) treatment have been made in the last decade, including the use of immunotherapy and, in particular, immune checkpoint inhibitors that have been shown to improve the survival of patients with triple negative BC. This narrative review summarizes the studies supporting the use of immunotherapy in BC. Furthermore, the usefulness of 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG) positron emission/computerized tomography (PET/CT) to image the tumor heterogeneity and to assess treatment response is explored, including the different criteria to interpret 2-[18F]FDG PET/CT imaging. The concept of immuno-PET is also described, by explaining the advantages of mapping treatment targets with a non-invasive and whole-body tool. Several radiopharmaceuticals in the preclinical phase are referred too, and, considering their promising results, translation to human studies is needed to support their use in clinical practice. Overall, this is an evolving field in BC treatment, despite PET imaging developments, the future trends also include expanding immunotherapy to early-stage BC and using other biomarkers.

Evaluation of Semiautomatic and Deep Learning-Based Fully Automatic Segmentation Methods on [18F]FDG PET/CT Images from Patients with Lymphoma: Influence on Tumor Characterization.

The objective is to assess the performance of seven semiautomatic and two fully automatic segmentation methods on [18F]FDG PET/CT lymphoma images and evaluate their influence on tumor quantification. All lymphoma lesions identified in 65 whole-body [18F]FDG PET/CT staging images were segmented by two experienced observers using manual and semiautomatic methods. Semiautomatic segmentation using absolute and relative thresholds, k-means and Bayesian clustering, and a self-adaptive configuration (SAC) of k-means and Bayesian was applied. Three state-of-the-art deep learning-based segmentations methods using a 3D U-Net architecture were also applied. One was semiautomatic and two were fully automatic, of which one is publicly available. Dice coefficient (DC) measured segmentation overlap, considering manual segmentation the ground truth. Lymphoma lesions were characterized by 31 features. Intraclass correlation coefficient (ICC) assessed features agreement between different segmentation methods. Nine hundred twenty [18F]FDG-avid lesions were identified. The SAC Bayesian method achieved the highest median intra-observer DC (0.87). Inter-observers' DC was higher for SAC Bayesian than manual segmentation (0.94 vs 0.84, p < 0.001). Semiautomatic deep learning-based median DC was promising (0.83 (Obs1), 0.79 (Obs2)). Threshold-based methods and publicly available 3D U-Net gave poorer results (0.56 ≤ DC ≤ 0.68). Maximum, mean, and peak standardized uptake values, metabolic tumor volume, and total lesion glycolysis showed excellent agreement (ICC ≥ 0.92) between manual and SAC Bayesian segmentation methods. The SAC Bayesian classifier is more reproducible and produces similar lesion features compared to manual segmentation, giving the best concordant results of all other methods. Deep learning-based segmentation can achieve overall good segmentation results but failed in few patients impacting patients' clinical evaluation.

The current role of nuclear medicine in breast cancer.

Breast cancer is the most common cancer in females worldwide. Nuclear medicine plays an important role in patient management, not only in initial staging, but also during follow-up. Radiopharmaceuticals to study breast cancer have been used for over 50 years, and several of these are still used in clinical practice, according to the most recent guideline recommendations.In this critical review, an overview of nuclear medicine procedures used during the last decades is presented. Current clinical indications of each of the conventional nuclear medicine and PET/CT examinations are the focus of this review, and are objectively provided. Radionuclide therapies are also referred, mainly summarising the methods to palliate metastatic bone pain. Finally, recent developments and future perspectives in the field of nuclear medicine are discussed. In this context, the promising potential of new radiopharmaceuticals not only for diagnosis, but also for therapy, and the use of quantitative imaging features as potential biomarkers, are addressed.Despite the long way nuclear medicine has gone through, it looks like it will continue to benefit clinical practice, paving the way to improve healthcare provided to patients with breast cancer.

Prediction of pathological response after neoadjuvant chemotherapy using baseline FDG PET heterogeneity features in breast cancer.

Complete pathological response to neoadjuvant systemic treatment (NAST) in some subtypes of breast cancer (BC) has been used as a surrogate of long-term outcome. The possibility of predicting BC pathological response to NAST based on the baseline 18F-Fluorodeoxyglucose positron emission tomography (FDG PET), without the need of an interim study, is a focus of recent discussion. This review summarises the characteristics and results of the available studies regarding the potential impact of heterogeneity features of the primary tumour burden on baseline FDG PET in predicting pathological response to NAST in BC patients. Literature search was conducted on PubMed database and relevant data from each selected study were collected. A total of 13 studies were eligible for inclusion, all of them published over the last 5 years. Eight out of 13 analysed studies indicated an association between FDG PET-based tumour uptake heterogeneity features and prediction of response to NAST. When features associated with predicting response to NAST were derived, these varied between studies. Therefore, definitive reproducible findings across series were difficult to establish. This lack of consensus may reflect the heterogeneity and low number of included series. The clinical relevance of this topic justifies further investigation about the predictive role of baseline FDG PET.

Joint EANM/SNMMI/ESTRO practice recommendations for the use of 2-[18F]FDG PET/CT external beam radiation treatment planning in lung cancer V1.0.

PURPOSE: 2-[18F]FDG PET/CT is of utmost importance for radiation treatment (RT) planning and response monitoring in lung cancer patients, in both non-small and small cell lung cancer (NSCLC and SCLC). This topic has been addressed in guidelines composed by experts within the field of radiation oncology. However, up to present, there is no procedural guideline on this subject, with involvement of the nuclear medicine societies. METHODS: A literature review was performed, followed by a discussion between a multidisciplinary team of experts in the different fields involved in the RT planning of lung cancer, in order to guide clinical management. The project was led by experts of the two nuclear medicine societies (EANM and SNMMI) and radiation oncology (ESTRO). RESULTS AND CONCLUSION: This guideline results from a joint and dynamic collaboration between the relevant disciplines for this topic. It provides a worldwide, state of the art, and multidisciplinary guide to 2-[18F]FDG PET/CT RT planning in NSCLC and SCLC. These practical recommendations describe applicable updates for existing clinical practices, highlight potential flaws, and provide solutions to overcome these as well. Finally, the recent developments considered for future application are also reviewed.

Perspective paper about the joint EANM/SNMMI/ESTRO practice recommendations for the use of 2-[18F]FDG-PET/CT external beam radiation treatment planning in lung cancer.

In "Joint EANM/SNMMI/ESTRO Practice Recommendations for the Use of 2-[18F]FDG-PET/CT External Beam Radiation Treatment Planning in Lung Cancer V1.0" clinical indications for PET-CT in (non-)small cell lung cancer are highlighted and selective nodal irradiation is discussed. Additionally, concepts about target definition, target delineation and treatment evaluation are reviewed.

Positron Emission Tomography-Derived Metrics Predict the Probability of Local Relapse After Oligometastasis-Directed Ablative Radiation Therapy.

PURPOSE: Early positron emission tomography-derived metrics post-oligometastasis radioablation may predict impending local relapses (LRs), providing a basis for a timely ablation. METHODS AND MATERIALS: Positron emission tomography data of 623 lesions treated with either 24 Gy single-dose radiation therapy (SDRT) (n = 475) or 3 ×  9 Gy stereotactic body radiation therapy (SBRT) (n = 148) were analyzed in a training data set (n = 246) to obtain optimal cutoffs for pretreatment maximum standardized uptake value (SUVmax) and its 3-month posttreatment decline (ΔSUVmax) in predicting LR risk, validated in a data set unseen to testing (n = 377). RESULTS: At a median of 21.7 months, 91 lesions developed LRs: 39 of 475 (8.2%) after SDRT and 52 of 148 (35.1%) after SBRT. The optimal cutoff values were 12 for SUVmax and -75% for ΔSUVmax. Bivariate SUVmax/ΔSUVmax permutations rendered a 3-tiered LR risk stratification of dual-favorable (low risk), 1 adverse (intermediate risk) and dual-adverse (high risk). Actuarial 5-year local relapse-free survival rates were 93.9% versus 89.6% versus 57.1% (P < .0001) and 76.1% versus 48.3% versus 8.2% (P < .0001) for SDRT and SBRT, respectively. The SBRT area under the ROC curve was 0.71 (95% CI, 0.61-0.79) and the high-risk subgroup yielded a 76.5% true positive LR prediction rate. CONCLUSIONS: The SBRT dual-adverse SUVmax/ΔSUVmax category LR prediction power provides a basis for prospective studies testing whether a timely ablation of impending LRs affects oligometastasis outcomes.

123I-FP-CIT SPECT in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease: a new quantitative analysis of autopsy confirmed cases.

PURPOSE: The aim of this study was to re-evaluate the differentiation of patients with dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and Parkinson's disease (PD) using a quantitative analysis of 123I-FP-CIT SPECT scans. METHODS: Thirty-six patients with in vivo 123I-FP-CIT SPECT and neuropathological diagnoses were included. Based on neuropathological criteria, patients were further subclassified into nine AD, eight DLB, ten PD and nine with other diagnoses. An additional 16 healthy controls (HC) scanned with 123I-FP-CIT SPECT were also included. All images were visually assessed as normal versus abnormal uptake by consensus of five nuclear medicine physicians. Bihemispheric mean was calculated for caudate binding potential (CBP), putamen binding potential (PBP) and putamen-to-caudate ratio (PCR). RESULTS: Patients with DLB had significantly lower CBP and PBP than patients with AD and significantly higher PCR than patients with PD. Qualitative visual analysis of the images gave an accuracy of 88% in the evaluation of the status of the nigrostriatal pathway considering all individuals, and 96% considering only the patients with PD, AD and DLB. Quantitative analyses provided a balanced accuracy of 94%, 94% and 100% in binary classifications DLB versus AD, DLB versus PD and PD versus AD, respectively, and an accuracy of 93% in the differentiation among patients with DLB, AD and PD simultaneously. No statistically significant differences were observed between the AD and HC. CONCLUSIONS: This study demonstrates a very high diagnostic accuracy of the quantitative analysis of(123I-FP-CIT SPECT data to differentiate among patients with DLB, PD and AD.

Warthin Tumor Incidentally Detected on PET/CT Showing Both 68Ga-DOTANOC and 18F-FDG Uptake.

ABSTRACT: A patient with moderately differentiated pancreatic neuroendocrine tumor with synchronous multifocal liver metastases was referred for further staging with PET/CT. The examinations were performed on 2 consecutive days and showed mild 68Ga-DOTANOC and intense 18F-FDG uptake in an incidental right parotid nodule. Differential diagnoses include primary or metastatic neuroendocrine tumor, malignant or benign primary parotid tumor, and intraparotid lymph node. Histology revealed characteristics of a Warthin tumor. While focal FDG uptake in Warthin tumor is frequently described, the somatostatin expression was rarely reported. This clinical case describes 68Ga-DOTANOC and 18F-FDG uptake in a parotid Warthin tumor histologically confirmed.

Are lesion features reproducible between 18F-FDG PET/CT images when acquired on analog or digital PET/CT scanners?

OBJECTIVES: To compare lesion features extracted from 18F-FDG PET/CT images acquired on analog and digital scanners, on consecutive imaging data from the same subjects. METHODS: Whole-body 18F-FDG PET/CT images from 55 oncological patients were acquired twice after a single 18F-FDG injection, with a digital and an analog PET/CT scanner, alternately. Twenty-nine subjects were examined first on the digital, and 26 first on the analog equipment. Image reconstruction was performed using manufacturer standard clinical protocols and protocols that fulfilled EARL1 specifications. Twenty-five features based on lesion standardized uptake value (SUV) and geometry were assessed. To compare these features, intraclass correlation coefficient (ICC), relative difference (RD), absolute value of RD (|RD|), and repeatability coefficient (RC) were used. RESULTS: In total, 323 18F-FDG avid lesions were identified. High agreement (ICC > 0.75) was obtained for most of the lesion features pulled out from both scanners' imaging data, especially when reconstruction protocols fulfilled EARL1 specifications. For EARL1 reconstruction images, the features frequently used in clinics, SUVmax, SUVpeak, SUVmean, metabolic tumor volume, and total lesion glycolysis, reached an ICC of 0.92, 0.95, 0.87, 0.98, and 0.98, and a median RD (digital-analog) of 3%, 5%, 4%, - 3% and 1%, respectively. Using standard reconstruction protocols, the ICC were 0.84, 0.93, 0.80, 0.98, and 0.98, and the RD were 20%, 11%, 13%, - 7%, and 7%, respectively. CONCLUSION: Under controlled acquisition and reconstruction parameters, most of the features studied can be used for research and clinical work. This is especially important for multicenter studies and patient follow-ups. KEY POINTS: • Using manufacturer standard clinical reconstruction protocols, lesions SUV was significantly higher when using the digital scanner, especially the SUVmax that was approximately 20% higher. • High agreement was obtained for the majority of the lesion features when using reconstruction protocols that fulfilled EARL1 specifications. • Longitudinal patient studies can be performed interchangeably between digital and analog scanners when both fulfill EARL1 specifications.

Nuclear medicine and molecular imaging advances in the 21st century.

Currently, Nuclear Medicine has a clearly defined role in clinical practice due to its usefulness in many medical disciplines. It provides relevant diagnostic and therapeutic options leading to patients' healthcare and quality of life improvement. During the first two decades of the 21stt century, the number of Nuclear Medicine procedures increased considerably.Clinical and research advances in Nuclear Medicine and Molecular Imaging have been based on developments in radiopharmaceuticals and equipment, namely, the introduction of multimodality imaging. In addition, new therapeutic applications of radiopharmaceuticals, mainly in oncology, are underway.This review will focus on radiopharmaceuticals for positron emission tomography (PET), in particular, those labeled with Fluorine-18 and Gallium-68. Multimodality as a key player in clinical practice led to the development of new detector technology and combined efforts to improve resolution. The concept of dual probe (a single molecule labeled with a radionuclide for single photon emission computed tomography)/positron emission tomography and a light emitter for optical imaging) is gaining increasing acceptance, especially in minimally invasive radioguided surgery. The expansion of theranostics, using the same molecule for diagnosis (γ or positron emitter) and therapy (ß minus or α emitter) is reshaping personalized medicine.Upcoming research and development efforts will lead to an even wider array of indications for Nuclear Medicine both in diagnosis and treatment.