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Abstract Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [18F]FDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published “Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [ 18 F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0”. These recommendations arose from a fruitful collaboration between international nuclear medicine societies and experts in cancer treatment. In this perspective, the key elements of the initiative are reported, summarizing the core aspects of the guidelines for radiologists and nuclear medicine physicians. Beyond the previous guidelines, this perspective adds further commentary on how this technology can advance development of novel therapeutic approaches and guide management of individual patients.

Abstract Purpose Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale (“Cuneo score”). Methods We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients’ information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. Results Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). Conclusions In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Artificial intelligence (AI) has become a pivotal tool for medical image analysis, significantly enhancing drug discovery through improved diagnostics, staging, prognostication, and response assessment. At a high level, AI-driven image analysis enables the quantification and synthesis of previously qualitative imaging characteristics, facilitating the identification of novel disease-specific biomarkers, patient risk stratification, prognostication, and adverse event prediction. In addition, AI can assist in response assessment by capturing changes in imaging "phenotype" over time, allowing for optimized treatment plans based on real-time analysis. Integrating this emerging technology into drug discovery pipelines has the potential to accelerate the identification and development of new pharmaceuticals by assisting in target identification and patient selection, as well as reducing the incidence, and therefore cost, of failed trials through high-throughput, reproducible, and data-driven insights. Continued progress in AI applications will shape the future of medical imaging, ultimately fostering more efficient, accurate, and tailored drug discovery processes. Herein, we offer a comprehensive overview of how AI enhances medical imaging to inform drug development and therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicolas Aide reports a relationship with Siemens Molecular Imaging that includes: funding grants. Michael A. Postow reports a consulting or advisory role from Bristol-Myers Squibb; Cancer Expert Now; Chugai Pharma; Eisai; Erasca, Inc; Intellisphere; Merck; MJH Associates; Nektar; Novartis; Pfizer; and WebMD and research funding from Array BioPharma (Inst); Bristol-Myers Squibb (Inst); Infinity Pharmaceuticals (Inst); Merck (Inst); Novartis (Inst); and Rgenix (Inst). Stephane Champiat: Honoraria: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck, Novartis and Roche. Principal Investigator of Clinical Trials for: Abbvie, Amgen, Boehringer Ingelheim, Cytovation, Eisai, Imcheck Therapeutics, Immunocore, Molecular Partners Ag, Merck, Ose Pharma, Pierre Fabre, Replimune, Sanofi Aventis, Seagen, Sotio A.S, Transgene. Advisory Board/Consulting: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, BioNTech, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom, Inc., Nanobiotix, Nextcure, Oncovita, Pierre Fabre, Seagen, Tatum Bioscience, Tollys SAS, UltraHuman8. Travel and congress: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Ose Pharma, Roche, Sotio. As part of the Drug Development Department (DITEP): Principal/sub-Investigator of Clinical Trials for Abbvie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Astex Pharmaceuticals, Astra Zeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Casi Pharmaceuticals, Inc, Celgene Corporation, Cellcentric, Chugai Pharmaceutical Co, Cullinan-Apollo, Curevarc, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Incyte Corporation, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Janssen R&D LLC, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Genomics, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre Medicament, Relay Therapeutics, Inc, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Transgene S.A, Turning Point Therapeutics, Xencor. Research Grants from Astrazeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi. Nonfinancial support (drug supplied) from Astrazeneca, BMS, Boehringer Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. Laurent Dercle was supported by RSNA Research & Education Foundation, through Canon Medical Systems, USA/RSNA Research Resident Grant. The content is solely the responsibility of the authors and does not necessarily represent the official views of the RSNA R&E Foundation.The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Malignant pleural mesothelioma (MPM) is the most frequent aggressive tumor affecting the pleura, accounting for over 38,000 deaths worldwide. It originates from the mesothelial cells and is mostly associated to asbestos exposure. Depending on the extent of the disease, the management of MPM varies from surgical intervention to a combination of systemic chemotherapy, immunotherapy, and radiation therapy. Major International scientific societies provide continuous updates on proper management of the disease, including recommendations on the optimal imaging algorithms, which are crucial for determining effective treatment options and optimizing clinical outcomes. However, despite the continuous efforts to improve patients' prognosis, median overall survival remains poor, ranging from 8 to 14 months. And even in case of initial response to treatment, local or distant recurrences represent almost a certainty, requiring appropriate imaging for the assessment of tumor sites. The aim of the present article is to illustrate the current status of imaging for staging and restaging of MPM, not forgetting most recent novelties in the diagnostic work-up of the disease., Competing Interests: Declaration of competing interest The author declares to have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Currently, risk stratification for pediatric Hodgkin lymphoma is based on clinical factors such as stage, bulk, and systemic symptoms. Novel minimally invasive biomarkers could enhance both prognosis and treatment strategies. Therefore, the plasma extracellular vesicles' microRNA profile was characterized by small RNA sequencing in 36 classical Hodgkin lymphoma cases and these findings were confirmed in an extended cohort of 86 patients by RT-qPCR. It was found that the levels of miR-122-5p at diagnosis were significantly higher (p -value: 0.0002) in patients who relapsed compared to patients in remission. The 5-year event-free survival of cases with high and low levels of miR-122-5p was 65 ± 7% and 93 ± 4%, respectively. MiR-122-5p levels were significantly associated with clinical events in both univariate (p -value: 0.0009) and multivariate (p -value: 0.0037) analysis (hazard ratio 5.8). Target prediction analysis suggests an involvement in the polarization of immune cells. The phenotypic characterization of peripheral blood mononuclear cells in 12 patients showed significantly increased levels of CD4+ T-cells in cases with high miR-122-5p levels as compared to low levels (p -value: 0.048). Moreover, CCL17 (TARC) and IL-6 plasma levels at diagnosis were significantly higher as compared to healthy donors (p -value: ≤0.0001). MiR-122-5p could complement current prognostic assays to identify patients at high risk of relapse.

Objectives: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has gained a primary role in prostate cancer (PCa) imaging, overcoming conventional imaging and prostate-specific antigen (PSA) serum levels, and has recently emerged as a promising technique for monitoring therapy response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with novel hormonal therapy, taxanes, and radioligand therapy (RLT). In this review, we aim to provide an overview of the most relevant aspects under study and future prospects related to the prognostic role of PSMA PET/CT in mCRPC., Methods: A systematic literature search was performed in the following databases: MEDLINE, PubMed, and EMBASE databases. The study focused exclusively on English-language studies, excluding papers not pertinent to the topic., Results: PSMA PET imaging offers a higher sensitivity and specificity than conventional imaging and provides accurate staging and efficient diagnosis of distant metastases. The data presented herein highlight the usefulness of PET in risk stratification, with a prognostic potential that can have a significant impact on clinical practice. Several prospective trials are ongoing and will shortly provide more evidence supporting the prognostic potential of PET PSMA data in this clinical scenario., Conclusions: Current evidence proves the prognostic role of PSMA PET/CT in different settings, with raising relevance also in the context of mCRPC.

The Food and Drug Administration and the European Medicines Agency have recently approved chimeric antigen receptor-engineered (CAR) T cells to treat several refractory/relapsed B-cell lymphomas. This comprehensive review aims to demonstrate the pivotal role that [ 18 F]-FDG PET/computed tomographic (CT) imaging can play to enhance the care of patients treated with CAR T-cell therapy. To this end, this review deciphers evidence showing the diagnostic, prognostic, predictive, and theragnostic value of [ 18 F]-FDG PET/CT-derived parameters., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Unspecific bone uptake (UBU) related to [ 18 F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [ 18 F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [ 18 F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUV max , SUV mean , PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HU mean ) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less ( n = 2) or more ( n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake ( n = 178) as PCa metastases or not. Results: In total, 448 bone [ 18 F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT ( P < 0.001) with determination of SUV max ( P < 0.001) and HU mean ( P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation ( n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score's AUC was significantly higher than that of HU mean (AUC, 0.62) and remained high among lesions with HU mean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [ 18 F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Systemic sclerosis (SSc) rarely overlaps with noninfective granulomatous conditions, such as sarcoidosis or pneumoconiosis. 1 A 73-year-old White man with anti-Scl70 positive SSc was evaluated for arthralgia, fever, and weight loss.

2-Deoxy-2-[ 18 F]fluoro- d -glucose PET/computed tomography ([ 18 F]FDG PET/CT) has proven to be a sensitive method for the detection and evaluation of hematologic malignancies, especially lymphoma. The increasing incidence and mortality rates of leukemia have raised significant concerns. Through the utilization of whole-body imaging, [ 18 F]FDG PET/CT provides a thorough assessment of the entire bone marrow, complementing the limited insights provided by biopsy samples. In this regard, [ 18 F]FDG PET/CT has the ability to assess diverse types of leukemia The utilization of [ 18 F]FDG PET/CT has been found to be effective in evaluating leukemia spread beyond the bone marrow, tracking disease relapse, identifying Richter's transformation, and assessing the inflammatory activity associated with acute graft versus host disease. However, its role in various clinical scenarios in leukemia remains unacknowledged. Despite their less common use, some novel PET/CT radiotracers are being researched for potential use in specific scenarios in leukemia patients. Therefore, the objectives of this review are to provide a thorough assessment of the current applications of [ 18 F]FDG PET/CT in the staging and monitoring of leukemia patients, as well as the potential for an expanding role of PET/CT in leukemia patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN)., Methods: This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled., Results: Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels ( p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers ( p = 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups., Conclusion: MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Al-Ibraheem, Abdlkadir, Al-Adhami, Lopci, Al-Omari, Al-Masri, Yousef, Al-Hajaj, Mohamad, Singer and Sykiotis.)

Introduction: The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging., Evidence Acquisition: A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations., Evidence Synthesis: Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident., Conclusions: PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.

The utilization of chimeric antigen receptor (CAR) T-cell therapy to target cluster of differentiation (CD)19 in cancer immunotherapy has been a recent and significant advancement. Although this approach is highly specific and selective, it is not without complications. Therefore, a systematic review was conducted to assess the current state of positron emission tomography (PET) in evaluating the adverse effects induced by CAR T-cell therapy. A thorough search of relevant articles was performed in databases such as PubMed, Scopus, and Web of Science up until March 2024. Two reviewers independently selected articles and extracted data, which was then organized and categorized using Microsoft Excel. The risk of bias and methodological quality was assessed. In total, 18 articles were examined, involving a total of 753 patients, in this study. A wide range of utilities were analyzed, including predictive, correlative, and diagnostic utilities. While positive outcomes were observed in all the mentioned areas, quantitative analysis of the included studies was hindered by their heterogeneity and use of varying PET-derived parameters. This study offers a pioneering exploration of this promising field, with the goal of encouraging further and more focused research in upcoming clinical trials.

Background: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [ 123 I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [ 123 I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [ 123 I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals., Methods: We searched the PubMed database for studies performing a head-to-head comparison between [ 123 I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([ 11 C]C-HED), 18 F-18F-3,4-dihydroxyphenylalanine ([ 18 F]DOPA) [ 124 I]mIBG and Meta-[18F]fluorobenzylguanidine ([ 18 F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA)., Results: Ten studies were selected: two regarding [ 11 C]C-HED, four [ 18 F]DOPA, one [ 124 I]mIBG, and three [ 18 F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [ 18 F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies., Conclusions: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination., (© 2023. The Author(s).)

In the last years, PSMA-PET imaging and multiparametric MRI (mpMRI) have improved the clinical management of prostate cancer (PCa) patients. Currently, mpMRI is recommended by the EAU (European Association of Urology) guidelines for the primary diagnosis of PCa, whereas PSMA-PET is reserved for disease staging, particularly in high risk localized or locally advanced disease, as well as for biochemical recurrence after surgery. Nevertheless, several studies have explored the added value of PSMA-PET in other clinical scenarios, including primary diagnosis and especially for the detection of clinically significant PCa (csPCa). In the present contribution, we will provide an overview and an update on the current literature on imaging detection of csPCa, with a particular focus on mpMRI, PSMA-PET and their comparison., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The primary objective of this study was to investigate the potential role of tissue osteopontin, also known as secreted phosphoprotein 1 ( SPP1 ), as a contributing factor to an unfavorable prognosis in classical Hodgkin's lymphoma (HL) patients who received the same treatment protocol. The study involved 44 patients aged 4-22 years, with a median follow-up period of 3 years. Patients with higher levels of SPP1 were associated with tissue necrosis and inflammation, and there was a trend toward a poorer prognosis in this group. Before therapy, we found a correlation between positron emission tomography (PET) scans and logarithmic SPP1 levels ( p = 0.035). However, the addition of SPP1 levels did not significantly enhance the predictive capacity of PET scans for recurrence or progression. Elevated SPP levels were associated with tissue mRNA counts of chemotactic and inflammatory chemokines, as well as specific monocyte/dendritic cell subtypes, defined by IL-17RB, PLAUR, CXCL8, CD1A, CCL13, TREM1 , and CCL24 markers. These findings contribute to a better understanding of the potential factors influencing the prognosis of HL patients and the potential role of SPP1 in the disease. While the predictive accuracy of PET scans did not substantially improve during the study, the results underscore the complexity of HL and highlight the relationships between SPP1 and other factors in the context of HL relapse.

Receptor tyrosine kinases, or RTKs, are one large family of cell surface receptors involved in signal transduction, which represent an integral part of the signaling pathways. They play a crucial role in most important cellular processes, starting with the cell cycle, proliferation and differentiation, as well as cell migration, metabolism and survival. The introduction of ImmunoPET evaluating the expression of RTKs by specific monoclonal antibodies (mAbs) or antibody fragments is regarded as a promising tool for imaging treatment efficacy and developing anticancer therapeutics. Our review focuses mainly on the current clinical research regarding ImmunoPET targeting RTKs, with particular interest in the epidermal growth factor family, or HER family, and vascular endothelial-derived growth factor/receptor.

In the last decade, monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or PD-L1 have been developed and immune checkpoint inhibitors (ICIs) have become the main approach in cancer immunotherapy. However, not all patients benefit from ICI therapy and some are at risk of developing treatment-induced side-effects. These aspects, in parallel with the imaging challenges related to response assessments during immunotherapy, have driven scientific research to the discovery of new predictive biomarkers to individualize patients who could benefit from ICIs. In this context, molecular imaging using PET (positron emission tomography), which allows for whole-body tumor visualization, may be a promising non-invasive method for the determination of patients' sensitivity to antibody drugs. Several PET tracers, diverse from 2-[ 18 F]FDG (or 2-Deoxy-2-[ 18 F]fluoroglucose), have been developed to image immune checkpoints (ICs) or key elements of the immune system, although most of them are still in preclinical phases. Herein, we present the current state of the ImmunoPET-targeting of IC proteins with mAbs and antibody fragments, with a main focus on the latest developments in clinical molecular imaging studies of solid tumors. Moreover, given the relevance of the immune system and of tumor-infiltrating lymphocytes in particular in the prediction of the benefit of ICIs, we dedicate a portion of this review to ImmunoPET-targeting T cells.

Standard-of-care medical imaging techniques such as CT, MRI, and PET play a critical role in managing patients diagnosed with metastatic cutaneous melanoma. Advancements in artificial intelligence (AI) techniques, such as radiomics, machine learning, and deep learning, could revolutionize the use of medical imaging by enhancing individualized image-guided precision medicine approaches. In the present article, we will decipher how AI/radiomics could mine information from medical images, such as tumor volume, heterogeneity, and shape, to provide insights into cancer biology that can be leveraged by clinicians to improve patient care both in the clinic and in clinical trials. More specifically, we will detail the potential role of AI in enhancing detection/diagnosis, staging, treatment planning, treatment delivery, response assessment, treatment toxicity assessment, and monitoring of patients diagnosed with metastatic cutaneous melanoma. Finally, we will explore how these proof-of-concept results can be translated from bench to bedside by describing how the implementation of AI techniques can be standardized for routine adoption in clinical settings worldwide to predict outcomes with great accuracy, reproducibility, and generalizability in patients diagnosed with metastatic cutaneous melanoma.

This retrospective study examines the diagnostic accuracy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) and neck magnetic resonance imaging (MRI) in detecting nodal metastasis for patients with laryngeal squamous cell carcinoma (LSCC) and assesses the predictive values of metabolic and structural features derived from 18 F-FDG PET/CT. By involving 66 patients from 2014 to 2021, the sensitivity and specificity of both modalities were calculated. 18 F-FDG PET/CT outperforms neck MRI for nodal disease detection, with 89% sensitivity, 65% specificity, and 77% accuracy for nodal metastasis ( p = 0.03). On the other hand, neck MRI had 66% sensitivity, 62% specificity, and 64% accuracy. Approximately 11% of patients witnessed a change in their therapy intent when relying on 18 F-FDG PET/CT nodal staging results. Analyzing the cohort for PET-derived metabolic and morphological parameters, a total of 167 lymph nodes (LN) were visualized. Parameters such as the LN maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN size were computed. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Among the 167 identified cervical LNs, 111 were histopathologically confirmed as positive. ROC analysis revealed the highest area under the curve for LN MTV (0.89; p < 0.01), followed by LN size (0.87; p < 0.01). Both MTV and LN size independently predicted LN metastasis through multivariate analysis. In addition, LN MTV can reliably predict false-positive LNs in preoperative staging, offering a promising imaging-based approach for further exploration.

[ 18 F]-FDG positron emission tomography with computed tomography (PET/CT) imaging is widely used to enhance the quality of care in patients diagnosed with cancer. Furthermore, it holds the potential to offer insight into the synergic effect of combining radiation therapy (RT) with immuno-oncological (IO) agents. This is achieved by evaluating treatment responses both at the RT and distant tumor sites, thereby encompassing the phenomenon known as the abscopal effect. In this context, PET/CT can play an important role in establishing timelines for RT/IO administration and monitoring responses, including novel patterns such as hyperprogression, oligoprogression, and pseudoprogression, as well as immune-related adverse events. In this commentary, we explore the incremental value of PET/CT to enhance the combination of RT with IO in precision therapy for solid tumors, by offering supplementary insights to recently released joint guidelines.

Purpose: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA., Methods: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study., Results: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis., Conclusion: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis., (© 2023. The Author(s).)

Immunotherapy has greatly improved the outcomes of patients with metastatic melanoma. However, it has also led to new patterns of response and progression, creating an unmet need for better biomarkers to identify patients likely to achieve a lasting clinical benefit or experience immune-related adverse events. In this study, we performed a focused literature survey covering the application of artificial intelligence (AI; in the form of radiomics, machine learning, and deep learning) to patients diagnosed with melanoma and treated with immunotherapy, reviewing 12 studies relevant to the topic published up to early 2022. The most commonly investigated imaging modality was CT imaging in isolation ( n = 9, 75.0%), while patient cohorts were most frequently recruited retrospectively and from single institutions ( n = 7, 58.3%). Most studies concerned the development of AI tools to assist in prognostication ( n = 5, 41.7%) or the prediction of treatment response ( n = 6, 50.0%). Validation methods were disparate, with two studies (16.7%) performing no validation and equal numbers using cross-validation ( n = 3, 25%), a validation set ( n = 3, 25%), or a test set ( n = 3, 25%). Only one study used both validation and test sets ( n = 1, 8.3%). Overall, promising results have been observed for the application of AI to immunotherapy-treated melanoma. Further improvement and eventual integration into clinical practice may be achieved through the implementation of rigorous validation using heterogeneous, prospective patient cohorts.

The purpose of this systematic review was to investigate the diagnostic accuracy of [ 18 F]FDG PET/CT and breast MRI for primary breast cancer (BC) response assessment after neoadjuvant chemotherapy (NAC) and to evaluate future perspectives in this setting. We performed a critical review using three bibliographic databases (i.e., PubMed, Scopus, and Web of Science) for articles published up to the 6 June 2023, starting from 2012. The Quality Assessment of Diagnosis Accuracy Study (QUADAS-2) tool was adopted to evaluate the risk of bias. A total of 76 studies were identified and screened, while 14 articles were included in our systematic review after a full-text assessment. The total number of patients included was 842. Eight out of fourteen studies (57.1%) were prospective, while all except one study were conducted in a single center. In the majority of the included studies (71.4%), 3.0 Tesla (T) MRI scans were adopted. Three out of fourteen studies (21.4%) used both 1.5 and 3.0 T MRI and only two used 1.5 T. [ 18 F]FDG was the radiotracer used in every study included. All patients accepted surgical treatment after NAC and each study used pathological complete response (pCR) as the reference standard. Some of the studies have demonstrated the superiority of [ 18 F]FDG PET/CT, while others proved that MRI was superior to PET/CT. Recent studies indicate that PET/CT has a better specificity, while MRI has a superior sensitivity for assessing pCR in BC patients after NAC. The complementary value of the combined use of these modalities represents probably the most important tool to improve diagnostic performance in this setting. Overall, larger prospective studies, possibly randomized, are needed, hopefully evaluating PET/MR and allowing for new tools, such as radiomic parameters, to find a proper place in the setting of BC patients undergoing NAC.

Breast cancer remains the most common cause of cancer death among women. Despite its considerable histological and molecular heterogeneity, those characteristics are not distinguished in most definitions of oligometastatic disease and clinical trials of oligometastatic breast cancer. After an exhaustive review of the literature covering all aspects of oligometastatic breast cancer, 35 experts from the European Organisation for Research and Treatment of Cancer Imaging and Breast Cancer Groups elaborated a Delphi questionnaire aimed at offering consensus recommendations, including oligometastatic breast cancer definition, optimal diagnostic pathways, and clinical trials required to evaluate the effect of diagnostic imaging strategies and metastasis-directed therapies. The main recommendations are the introduction of modern imaging methods in metastatic screening for an earlier diagnosis of oligometastatic breast cancer and the development of prospective trials also considering the histological and molecular complexity of breast cancer. Strategies for the randomisation of imaging methods and therapeutic approaches in different subsets of patients are also addressed., Competing Interests: Declaration of interests DEO-L reports honoraria from BMUC and unrestricted grants from Janssen for consensus nuclear medicine meetings in 2020 and 2022, outside the submitted work. LF reports grants from Bristol Myers Squibb and Banque Publique d’Investissement; honoraria for lectures from GE Healthcare, Fujifilm, and Median Technologies; support for attending meetings from Guerbet; participation on a safety monitoring board with Pandas Prodige; and research collaborations with Philips, Ariana Pharma, Evolucare, and Dassault Systems, outside the submitted work. EL reports royalties or licences from Springer, outside the submitted work. DK reports grants from Merck and honoraria from Merck Sharp & Dohme and Pfizer, outside the submitted work. SK reports an advisory role and study material from Novartis, Amgen, Somatex, Daiichi Sankyo, Gilead, AstraZeneca, Pfizer, Eli Lilly, MSD, and Roche for the submitted work; consulting fees from Eli Lilly and MSD; honoraria from AstraZeneca, Eli Lilly, and Pfizer; support for attending meetings from Roche, Daiichi Sankyo, and Eli Lilly; participation on boards with Novartis, Amgen, Somatex, pfm medical, MSD, Daiichi Sankyo, Seagen, Gilead Science, Agendia, Exact Science, Roche, Sonoscape, Eli Lilly, AstraZeneca, and Pfizer; and leadership in other boards with AGO, WSG, and ESMO, outside the submitted work. IM reports honoraria supported by Eli Lilly, Novartis, Pfizer, Seagen, Gilead, and Accuray, outside the submitted work. WMHO reports grants from Pfizer and AstraZeneca, travel grants from Daiitchi, and participation on an advisory board with GE, outside the submitted work. KH reports personal fees from Bayer, Sofie Biosciences, SIRTEX, Adacap, Curium, Endocyte, IPSEN, Siemens Healthineers, GE Healthcare, Amgen, Novartis, Y-mAbs, Aktis Oncology, Theragnostics, Pharma15, Debiopharm, AstraZeneca, and Janssen; non-financial support from ABX; and grants and personal fees from BTG, outside the submitted work. FC reports honoraria from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck Sharp, Meus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, priME Oncoloy, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, and Touchime, and support for attending meetings from Pfizer and Roche, outside the submitted work. BL reports participation on boards for AstraZeneca, Pfizer, Eli Lilly, Daiichi-Sankyo, Novartis, Pierre Fabre, Breast International Group Executive Committee, EORTC Breast Cancer Group, and Swedish Association of Breast Oncologists, outside the submitted work. WK reports consulting fees from Mint Medical and honoraria from Bristol Myers Squibb, outside the submitted work. CD reports consulting fees from Terumo, Sitex, and PSI CRO; honoraria from Ipsen; and a chairing role for EORTC Imaging Group, outside the submitted work. ES reports royalties from Springer; honoraria from Cancerodigest, Curio Science, Egis, Eli Lilly, Exact Sciences, Gilead, high5md, MSD, Novartis, and Pfizer; support for attending meetings from Egis, Gilead, Novartis, Pfizer, and Roche; participation on boards with AstraZeneca, Eli Lilly, Exact Sciences, Novartis, Oncompass Medicine, and Stowarzyszenie Rozowy Motyl; stock options from AstraZeneca, Eli Lilly, and Pfizer; receipt of equipment from AstraZeneca and Eli Lilly; and interests with Amgen, AstraZeneca, Eli Lilly, Novartis, OBI Pharma, Pfizer, Roche, and Samsung, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice., Competing Interests: Declaration of interests IB has received research grants from Dosisoft, GE Healthcare, and Siemens Healthineers, and is a member of the Society of Nuclear Medicine and Molecular Imaging Artificial Intelligence Task Force. BC has received research support from GWT and Technical University of Dresden, and won a 2021 Gilead Oncology Award to support his research; has received consulting fees from and is on the data safety monitoring board for Roche, BMS, Regeneron, and ADC; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, BMS, and Astra Zeneca; has received support for travel from Gilead; has submitted patents for molecular subclassification of DLBCL; and declares that he is a speaker of the Aggressive Lymphoma working group and is a steering board member of the German Lymphoma Alliance. UD has received institutional funding from Celgene and has served as a member of the Data Safety Monitoring Board for Amgen and Avencell Europe. EL has received grants from AIRC and the Italian Ministry of Health, royalties from Springer, and honoraria for lectures at the European Society of Molecular Imaging, Therapy and Molecular Imaging, and Therapy congresses. MN has received a research grant from Takeda. PR-O has received honoraria from Amgen, Bristol-Myers Squibb, Glaxo SmithKline, Janssen, Regeneron, and Sanofi, and has served as a member of the data safety monitoring board for Bristol-Myers Squibb, Glaxo SmithKline, Janssen, Oncopeptides, Pfizer, Sanofi, and Takeda. EZ has received honoraria from Amgen, Bristol Myers Squibb, Janssen, and Takeda. PLZ has received honoraria from and has participated on advisory boards or data safety monitoring boards for AstraZeneca, Beigene, Bristol Myers Squibb, Eusapharma, Gilead, Incyte, Janssen, Kyowa Kirin, Merck, Mundipharma, Novartis, Roche, Sanofi, and Takeda. KH reports personal fees from Adacap, Ktis Oncology, Amgen, Bayer, Curium, Endocyte, Ipsen, GE Healthcare, Novartis, Pharma15, Siemens Healthineers, SIRTEX, Theragnostics, and ymabs; personal fees and other from Sofie Biosciences; grants and personal fees from BTG; and non-financial support from ABX outside the submitted work. JK has received consulting fees from Telix and has served as a member of the data safety monitoring board for Novartis. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the past decade, the implementation of immunotherapy with checkpoint inhibitors has determined a major change in the management of oncological patients. The challenges associated to the new therapeutic regimen have promoted adapted criteria for response assessment to interpret imaging findings and atypical patterns of response. Parallel to the new morphological criteria, also 18 fluoro-deoxyglucose positron emission/computed tomography imaging has required novel approaches and specific guidelines on how to perform, interpret, and report the scan in patients with solid tumors under immune checkpoint inhibitors therapy. A summary of the novelties related to the new joint international European Association of Nuclear Medicine (EANM)/Society of Nuclear Medicine and Molecular Imaging (SNMMI)/Australian and New Zealand Society of Nuclear Medicine (ANZSNM) guidelines on immunotherapy is provided herein to elucidate most critical aspects in image interpretation.

Over the last several years, molecular imaging has gained a primary role in the evaluation of patients with brain metastases (BM). Therefore, the "Response Assessment in Neuro-Oncology" (RANO) group recommends amino acid radiotracers for the assessment of BM. Our review summarizes the current use of positron emission tomography (PET) radiotracers in patients with BM, ranging from present to future perspectives with new PET radiotracers, including the role of radiomics and potential theranostics approaches. A comprehensive search of PubMed results was conducted. All studies published in English up to and including December 2022 were reviewed. Current evidence confirms the important role of amino acid PET radiotracers for the delineation of BM extension, for the assessment of response to therapy, and particularly for the differentiation between tumor progression and radionecrosis. The newer radiotracers explore non-invasively different biological tumor processes, although more consistent findings in larger clinical trials are necessary to confirm preliminary results. Our review illustrates the role of molecular imaging in patients with BM. Along with magnetic resonance imaging (MRI), the gold standard for diagnosis of BM, PET is a useful complementary technique for processes that otherwise cannot be obtained from anatomical MRI alone.

Advanced melanoma is one of the deadliest cancers, owing to its invasiveness and its propensity to develop resistance to therapy. Surgery remains the first-line treatment for early-stage tumors but is often not an option for advanced-stage melanoma. Chemotherapy carries a poor prognosis, and despite advances in targeted therapy, the cancer can develop resistance. CAR T-cell therapy has demonstrated great success against hematological cancers, and clinical trials are deploying it against advanced melanoma. Though melanoma remains a challenging disease to treat, radiology will play an increasing role in monitoring both the CAR T-cells and response to therapy. We review the current imaging techniques for advanced melanoma, as well as novel PET tracers and radiomics, in order to guide CAR T-cell therapy and manage potential adverse events.