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.

2-[18F]FDG PET-based quantification of lymph node metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer.

BACKGROUND AND PURPOSE: The pre-surgical estimation of lymph node (LN) metastasis in colorectal cancer (CRC) poses a significant diagnostic predicament. The associations between LN morphology, density, and metabolic heterogeneity and LN metastasis status in CRCs have been seldomly examined through the lens of radiomics. This research aimed to assess 2-[18F]FDG PET-based quantification of intratumoral metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer. MATERIALS AND METHODS: The construction of the model utilized data from 264 CRC patients, all of whom underwent preoperative 2-[18F]FDG PET/CT. Radiomic features were extracted from PET and CT images of LNs. Least absolute shrinkage and selection operator (LASSO) regression was implemented for selecting pertinent imaging features with a tenfold cross-validation. The predictive accuracy for LN metastasis status was juxtaposed against traditional methodologies (comprising CT-reported LN status and PET/CT-reported LN status) by deploying the receiver operating characteristic (ROC) curve analysis. The radiomics signature was evaluated based on discrimination, calibration, and clinical utility parameters. The model was further subjected to validation using an independent cohort of 132 patients from the period of January 2012 to June 2020. RESULTS: The radiomics model was composed of eight significant radiomic features (five from PET and three from CT), encapsulating metabolic and density heterogeneity. The radiomics signature (area under the curve (AUC), 0.908) showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.563, P < 0.001) and PET/CT-reported LN status (AUC, 0.64, P < 0.001) for predicting LN-positive or LN-negative status. The radiomics signature (AUC, 0.885) also showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.587, P < 0.001) and PET/CT-reported LN status (AUC, 0.621, P < 0.001) to identify N1 and N2. This signature maintained its independence from clinical risk factors and exhibited robustness in the validation test set. Decision curve analysis attested to the clinical utility of the radiomics signature. CONCLUSIONS: The radiomics signature based on 2-[18F]FDG PET/CT, which derived image features directly from LNs irrespective of clinical risk factors, displayed enhanced diagnostic performance compared to conventional CT or PET/CT-reported LN status. This allows for the identification of pre-surgical LN metastasis status and facilitates a patient-specific prediction of LN metastasis status in CRC patients.

Prospective validation of the role of PET/CT in detecting disease after neoadjuvant chemotherapy in advanced ovarian cancer.

OBJECTIVES: The study aimed to compare the diagnostic accuracies of 2-[18F]FDG PET/CT and contrast-enhanced CT (ceCT) after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer (OC). MATERIALS AND METHODS: This study consisted historical observational cohort and prospective validation cohort. Patients with newly diagnosed stage III-IV OC scheduled for NACT were recruited, with imaging performed after three to six cycles of NACT before interval debulking surgery. Nineteen regions in the abdominopelvic cavity were scored for the presence and absence of disease, referenced to the intra-operative findings or histological specimens. Diagnostic metrics were compared using McNemar's test. RESULTS: In the historical cohort (23 patients, age 58 ± 13), 2-[18F]FDG PET had an overall accuracy (Acc) 82%, sensitivity (Sen) 38%, specificity (Spe) 97%, positive predictive value (PPV) 79% and negative predictive value (NPV) 82%; ceCT had an overall Acc 86%, Sen 64%, Spe 93%, PPV 75% and NPV 89%. In the prospective cohort (46 patients, age 59 ± 9), 2-[18F] FDG PET had an overall Acc 87%, Sen 48%, Spe 98%, PPV 84% and NPV 88%; ceCT had an overall Acc 89%, Sen 66%, Spe 95%, PPV 77% and NPV 91%. No significant difference was demonstrated between the two imaging modalities (p > 0.05). High false-negative rates were observed in the right subdiaphragmatic space, omentum, bowel mesentery and serosa. High omental metabolic uptake after NACT was associated with histological non-responders (p < 0.05). CONCLUSION: 2-[18F]FDG PET/CT had no additional value over ceCT with comparable diagnostic accuracy in detecting disease after NACT in advanced OC. CLINICAL RELEVANCE STATEMENT: 2-[18F]FDG PET/CT is not superior to contrast-enhanced CT in determining disease after neoadjuvant chemotherapy in advanced ovarian cancer; contrast-enhanced CT should be suffice for surgical planning before interval debulking surgery. KEY POINTS: • Additional value of 2-[18F]FDG PET/CT over contrast-enhanced CT is undefined in detecting disease after neoadjuvant chemotherapy. • 2-[18F]FDG PET/CT has comparable diagnostic accuracy compared to contrast-enhanced CT. • Contrast-enhanced CT will be suffice for surgical planning after neoadjuvant chemotherapy.

Endocrinology application of molecular imaging: current role of PET/CT.

BACKGROUND: In recent years, nuclear medicine imaging methods have proven to be of paramount importance in a wide variety of diseases, particularly in oncology, where they are crucial for assessing the extent of disease when conventional methods fall short. Moreover, nuclear imaging modalities are able to better characterize lesions using target agents related to specific pathways (e.g. glucose metabolism, cellular proliferation, amino acid transport, lipid metabolism, specific receptor ligands). The clinical presentation of endocrine diseases encompasses a broad spectrum of sign and symptoms. Moreover, endocrine tumors show varying degrees of aggressiveness from well differentiated and indolent to highly aggressive cancers, respectively. RATIONALE: With the application of new medicinal radio-compounds and increasingly advanced tomographic imaging technology, the utility of Positron Emission Tomography/Computed Tomography (PET/CT) in the field of endocrine diseases is expanding. AIM: This review aims to analyze and summarize the primary indications of PET/CT, providing a practical approach for clinicians. A comprehensive literature search on PubMed was conducted to provide an updated overview of the available evidence regarding the use of PET/CT in endocrinology. Within this review, we will discuss the applications of PET/CT, compare different radiopharmaceuticals and highlight the uptake mechanism, excluding neuroendocrine carcinomas from discussion. CONCLUSIONS: PET/CT is a valuable tool in diagnosing and managing endocrine disorders due to its capacity to furnish both functional and anatomical information, facilitate early lesion detection, guide treatment decisions, and monitor treatment response. Its non-invasive nature and precision make it an integral component of modern endocrine healthcare. This review aims to provide physicians with a clear perspective on the role of PET/CT imaging, discussing its emerging opportunities and appropriateness of use in endocrinological diseases.

[18F]FAPI-42 PET/CT in differentiated thyroid cancer: diagnostic performance, uptake values, and comparison with 2-[18F]FDG PET/CT.

PURPOSE: This study aimed to assess the diagnostic performance of [18F]FAPI-42 PET/CT and compare it with that of 2-[18F]FDG PET/CT in patients with differentiated thyroid cancer (DTC) with biochemical elevations in Tg or anti-Tg antibodies. METHODS: A total of 42 patients with DTC with biochemical elevations in Tg or anti-Tg antibodies underwent [18F]FAPI-42 PET/CT as part of this study; of which, 11 additionally underwent 2-[18F]FDG PET/CT within 7 days. Images were semi-quantitatively and visually interpreted, and the quantity, location, and uptake values of lesions were noted. The diagnostic capacity of [18F]FAPI-42 PET/CT and biomarkers affecting the uptake of [18F]FAPI-42 were evaluated. In addition, the diagnostic performance and uptake of [18F]FAPI-42 and 2-[18F]FDG were compared, and the correlation between lesion diameter and quantitative parameters was investigated. RESULTS: A total of 161 lesions were detected in 27 (64%) patients on [18F]FAPI-42 PET/CT. FAPI-positive local recurrence showed the highest uptake intensity, followed by lymphatic, other site-associated (bone and pleura), and pulmonary lesions (mean SUVmax, 4.7 versus 3.7 versus 3.0 versus 2.2, respectively; P < 0.0001). The levels of TSH, Tg, and Tg-Ab did not affect the uptake value of lesions (median SUVmax: 2.4 versus 3.2, P = 0.56; 2.9 versus 2.4, P = 0.0935; 2.8 versus 2.6, P = 0.0525, respectively). A total of 90 positive lesions were detected in 7 patients using both modalities. All positive lesions showed statistically higher uptake of 2-[18F]FDG than that of [18F]FAPI-42 (SUVmax, 2.6 versus 2.1; P = 0.026). However, the SUVmax of [18F]FAPI-42 was higher than that of 2-[18F]FDG in local recurrences and lymphatic lesions (SUVmax, 4.2 versus 2.9 and 3.9 versus 3.4, respectively; P > 0.05). CONCLUSION: [18F]FAPI-42 can be used for detecting lesions and reflecting FAP expression during local recurrence and metastasis in patients with DTC with biochemical elevations in Tg or anti-Tg antibodies. The diagnostic performance of [18F]FAPI-42 PET/CT is comparable with that of 2-[18F]FDG PET/CT in such patients.

Head-to-head comparison of [68Ga]Ga-P16-093 and 2-[18F]FDG PET/CT in patients with clear cell renal cell carcinoma: a pilot study.

PURPOSE: This pilot study was prospectively designed to evaluate and compare the diagnostic value of PET/CT using a PSMA-specific tracer [68Ga]Ga-P16-093 and a glucose metabolism probe 2-[18F]FDG in clear cell renal cell carcinoma (ccRCC) patients. METHODS: Forty-two pathologically confirmed ccRCC patients were included. Within 1 week, each patient underwent [68Ga]Ga-P16-093 and 2-[18F]FDG PET/CT. In addition to visual analysis of tumor number, the standardized uptake value (SUV) was measured for semiquantitative comparison and correlation analysis. RESULTS: For primary ccRCC patients, [68Ga]Ga-P16-093 PET/CT demonstrated a significantly higher detection rate (19/22 vs. 13/22, P = 0.031) and higher tumor uptake (15.7 ± 9.0 vs. 5.1 ± 3.4, P < 0.001) than 2-[18F]FDG PET/CT. In addition, the SUVmax of the primary tumor on [68Ga]Ga-P16-093 and 2-[18F]FDG PET/CT was significantly correlated with pT stage (for [68Ga]Ga-P16-093, r = 0.550, P = 0.008; for 2-[18F]FDG, r = 0.514, P = 0.014) and WHO/ISUP grade (for [68Ga]Ga-P16-093, r = 0.566, P = 0.006; for 2-[18F]FDG, r = 0.492, P = 0.020), respectively. For metastatic ccRCC patients, [68Ga]Ga-P16-093 PET/CT also demonstrated a better detection rate (21/22 vs. 14/22, P = 0.008) and higher tumor uptake (11.0 ± 6.4 vs. 4.4 ± 2.7, P < 0.001) than 2-[18F]FDG PET/CT. The SUVmax on [68Ga]Ga-P16-093 PET/CT had a significant association with PSMA expression in primary ccRCC (r = 0.776, P < 0.001) and metastatic ccRCC (r = 0.626, P = 0.029). CONCLUSIONS: [68Ga]Ga-P16-093 PET/CT demonstrates significantly better tumor detectability than 2-[18F]FDG PET/CT for ccRCC patients. TRIAL REGISTRATION: 68Ga-P16-093 and 18F-FDG PET/CT Imaging in the Same Group of Clear Cell Renal Cell Carcinoma Patients (NCT05432947, Registered 27 June 2021, retrospectively registered) URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT05432947 .

Comparison of whole-body DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis.

PURPOSE: To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). METHODS: Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. RESULTS: Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). CONCLUSION: Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.

Role of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography as survival predictor in amyotrophic lateral sclerosis.

PURPOSE: The identification of prognostic tools in amyotrophic lateral sclerosis (ALS) would improve the design of clinical trials, the management of patients, and life planning. We aimed to evaluate the accuracy of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography (2-[18F]FDG-PET) as an independent predictor of survival in ALS. METHODS: A prospective cohort study enrolled 418 ALS patients, who underwent brain 2-[18F]FDG-PET at diagnosis and whose survival time was available. We discretized the survival time in a finite number of classes in a data-driven fashion by employing a k-means-like strategy. We identified "hot brain regions" with maximal power in discriminating survival classes, by evaluating the Laplacian scores in a class-aware fashion. We retained the top-m features for each class to train the classification systems (i.e., a support vector machine, SVM), using 10% of the ALS cohort as test set. RESULTS: Data were discretized in three survival profiles: 0-2 years, 2-5 years, and > 5 years. SVM resulted in an error rate < 20% for two out of three classes separately. As for class one, the discriminant clusters included left caudate body and anterior cingulate cortex. The most discriminant regions were bilateral cerebellar pyramid in class two, and right cerebellar dentate nucleus, and left cerebellar nodule in class three. CONCLUSION: Brain 2-[18F]FDG-PET along with artificial intelligence was able to predict with high accuracy the survival time range in our ALS cohort. Healthcare professionals can benefit from this prognostic tool for planning patients' management and follow-up. 2-[18F]FDG-PET represents a promising biomarker for individual patients' stratification in clinical trials. The lack of a multicentre external validation of the model warrants further studies to evaluate its generalization capability.

Diagnostic relevance of 2-[18 F]-FDG PET/CT in patients recently diagnosed with monoclonal gammopathy of undetermined significance.

2-[18 F]-FDG PET/CT is a useful diagnostic technique to assess bone and soft tissue disease in multiple myeloma (MM) but is not recommended by the International Myeloma Working Group for the evaluation of monoclonal gammopathy of undetermined significance (MGUS). The objective of this study was to evaluate the role of 2-[18 F]-FDG PET/CT in the management of these patients. An observational retrospective study was conducted on 338 patients with MGUS who underwent 2-[18 F]-FDG PET/CT. The mean age was 70.80 ± 11.84 years, and 69.2% of patients had cardiovascular risk factors. Patients were classified according to their progression risk (Mayo Clinic). The mean post-diagnosis follow-up was 8.35 ± 14.46 months. Pathological findings were recorded in 49 patients: 30 with myeloma bone lesions (15 in the initial study and 15 in follow-up) and 19 with other neoplastic (n = 13) or pathologically significant findings (n = 6). Body mass index, monoclonal component rate (MCR) > 1 g/dL and ≥1 risk factors for MM were significant in univariate logistic regression analyses. The MCR emerged as the main predictor of a positive 2-[18 F]-FDG PET/CT in adjusted multivariate regression analysis, with an area under the receiver operating characteristic curve of 0.785 and cutoff for optimal sensitivity/specificity of 1.0 ng/mL (71.4% sensitivity, 71.2% specificity). 2-[18 F]-FDG PET/CT results correctly classify patients with MGUS and could improve the detection of bone lesions over existing techniques, with the additional possibility of detecting neoplastic processes. The best parameter to predict a positive 2-[18 F]-FDG PET/CT was the MCR.

Higher accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT comparing with 2-[18F]FDG PET/CT in clinical staging of NSCLC.

PURPOSE: This study aimed to explore the clinical staging performance of [68 Ga]Ga-DOTA-FAPI-04 PET/CT compared with that of 2-[18F]FDG PET/CT in non-small cell lung cancer (NSCLC) patients lesion by lesion. METHODS: A total of 134 diagnosed or suspected NSCLC patients were enrolled in the prospective study (ChiCTR2000038080); they received paired 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT. Of these patients, the retrospective analysis of 74 NSCLC patients with pathological results was conducted from primary tumor (T) diagnosis, lymph node (N), and metastatic lesion (M) staging. The imaging characteristics of the lung nodules and suspected metastases were obtained and analyzed, and the staging performance of 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT was compared. RESULTS: For T diagnosis, [68 Ga]Ga-DOTA-FAPI-04 showed better diagnostic performance than 2-[18F]FDG in 79 lung nodules of 72 patients, especially for nonsolid and small-dimension adenocarcinoma nodules. For N staging, 98 lymph nodes (LNs) with pathological results in 37 patients were analyzed. The SUVmax of [68 Ga]Ga-DOTA-FAPI-04 in the nonmetastatic LNs was significantly lower than that in the metastatic LNs. Regarding metastatic LN identification, the calculated optimum cut-off value of [68 Ga]Ga-DOTA-FAPI-04 SUVmax was 5.5, and the diagnostic accuracy using [68 Ga]Ga-DOTA-FAPI-04 and 2-[18F]FDG criteria was 94% and 30%, respectively (P < 0.001). For M staging, [68 Ga]Ga-DOTA-FAPI-04 identified more lesions than 2-[18F]FDG (257 vs. 139 lesions) in 14 patients with multiple metastases. Overall, the staging accuracy of [68 Ga]Ga-DOTA-FAPI-04 was better than that of 2-[18F]FDG in 52 patients with different pathological stages [43/52 (82.7%) vs. 27/52 (51.9%), P = 0.001]. CONCLUSION: Compared with 2-[18F]FDG PET/CT, [68 Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated better staging performance in NSCLC patients with different pathological stages, especially those with localized disease.

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.

Clinical and prognostic role of 2-[18F]FDG PET/CT and sarcopenia in treatment-naïve patients with T-cell lymphoblastic lymphoma.

T-cell lymphoblastic lymphoma (T-LBL) is a rare and highly aggressive non-Hodgkin lymphoma. This study aimed to explore the role of 2-[18F]FDG PET/CT, sarcopenia, clinical features, and treatment regimens in 49 treatment-naïve patients with T-LBL, and assess their predictive value in the prognosis. Sarcopenia was measured as skeletal muscle index (SMI) at L3 level from the CT component of PET/CT images. All 49 patients (35 males, 14 females; median age, 26 years [range, 3-66 years]) were enrolled in this study, including 36 adult patients and 13 pediatric patients. Lymph nodes, thymus, bone marrow, and pleura were the most common involved sites of T-LBL. The median SUVmax, MTV, and TLG of all lesions in these 49 patients were 12.4 (range, 4.2-40.5), 532.6 (17.4-3518.1), and 2112.2 (53.9-18,699.2), respectively. Eighteen out of 49 patients (36.7%) were diagnosed with sarcopenia. Sarcopenia patients had lower BMI and SUVmax of muscle at L3 level than non-sarcopenia patients (P < 0.05). Univariate Cox regression analysis indicated that higher MTV and TLG and intrathecal therapy (IT) were associated with longer progression-free survival (PFS) and overall survival (OS), while multivariate Cox regression analysis showed that TLG and IT were independent predictors for PFS, and only IT was an independent predictor for OS. In conclusion, low BMI and SUVmax of muscle at L3 level correlated with sarcopenia in T-LBL patients. Higher initial MTV and TLG and receiving IT were associated with better prognosis in T-LBL patients. TLG and IT, but not sarcopenia, were independent prognostic factors.

Diagnostic Accuracy of 2-[18F]FDG-PET and whole-body DW-MRI for the detection of bone marrow metastases in children and young adults.

OBJECTIVES: To compare the diagnostic accuracy of 2-[18F]fluoro-2-deoxy-D-glucose-enhanced positron emission tomography (2-[18F]FDG-PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection of bone marrow metastases in children and young adults with solid malignancies. METHODS: In this cross-sectional single-center institutional review board-approved study, we investigated twenty-three children and young adults (mean age, 16.8 years ± 5.1 [standard deviation]; age range, 7-25 years; 16 males, 7 females) with 925 bone marrow metastases who underwent 66 simultaneous 2-[18F]FDG-PET and DW-MRI scans including 23 baseline scans and 43 follow-up scans after chemotherapy between May 2015 and July 2020. Four reviewers evaluated all foci of bone marrow metastasis on 2-[18F]FDG-PET and DW-MRI to assess concordance and measured the tumor-to-bone marrow contrast. Results were assessed with a one-sample Wilcoxon test and generalized estimation equation. Bone marrow biopsies and follow-up imaging served as the standard of reference. RESULTS: The reviewers detected 884 (884/925, 95.5%) bone marrow metastases on 2-[18F]FDG-PET and 893 (893/925, 96.5%) bone marrow metastases on DW-MRI. We found different "blind spots" for 2-[18F]FDG-PET and MRI: 2-[18F]FDG-PET missed subcentimeter lesions while DW-MRI missed lesions in small bones. Sensitivity and specificity were 91.0% and 100% for 18F-FDG-PET, 89.1% and 100.0% for DW-MRI, and 100.0% and 100.0% for combined modalities, respectively. The diagnostic accuracy of combined 2-[18F]FDG-PET/MRI (100.0%) was significantly higher compared to either 2-[18F]FDG-PET (96.9%, p < 0.001) or DW-MRI (96.3%, p < 0.001). CONCLUSIONS: Both 2-[18F]FDG-PET and DW-MRI can miss bone marrow metastases. The combination of both imaging techniques detected significantly more lesions than either technique alone. KEY POINTS: • DW-MRI and 2-[18F]FDG-PET have different strengths and limitations for the detection of bone marrow metastases in children and young adults with solid tumors. • Both modalities can miss bone marrow metastases, although the "blind spot" of each modality is different. • A combined PET/MR imaging approach will achieve maximum sensitivity and specificity for the detection of bone marrow metastases in children with solid tumors.

Accurate preoperative staging with [68Ga]Ga-FAPI PET/CT for patients with oral squamous cell carcinoma: a comparison to 2-[18F]FDG PET/CT.

OBJECTIVE: To evaluate the potential value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in preoperative staging for patients with oral squamous cell carcinoma (OSCC) as compared to 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET/CT. METHODS: Thirty-six treatment-naïve patients with OSCC who underwent 2-[18F]FDG and [68Ga]Ga-FAPI PET/CT for preoperative staging were enrolled. The maximum standardised uptake value (SUVmax) of the primary tumour and suspected cervical metastatic lymph nodes, and the tumour-to-background ratio (TBR) of the primary tumour, were measured. The accuracy of two imaging modalities for preoperative diagnosis of metastatic lymph nodes was analysed. Histopathology served as the standard of reference. RESULTS: Thirty-seven primary lesions of 36 patients were accurately detected by both [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT. Regarding primary tumours, the SUVmax and TBR of the two imaging modalities in stage T3-T4 were significantly higher than those of stage T1-T2 (all p < 0.05). On the patient analysis, the accuracy for the evaluation of N1-N3 neck status was 52.6% (10/19) for [68Ga]Ga-FAPI PET/CT and 57.9% (11/19) for 2-[18F]FDG PET/CT. Notably, the accuracy for the evaluation of the N0 neck status between [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT was 100% (17/17) and 29% (5/17), respectively. Based on the patient, neck side and neck level, [68Ga]Ga-FAPI PET/CT resulted in higher specificity and accuracy in diagnosing metastatic neck lymph nodes than 2-[18F]FDG PET/CT (all p < 0.05). CONCLUSION: [68Ga]Ga-FAPI PET/CT is a promising tool for preoperative staging of OSCC, and appears to reduce the false positivity seen with 2-[18F]FDG PET/CT for the detection of neck lymph node metastases. KEY POINTS: • [68Ga]Ga-FAPI PET/CT is a promising tool targeting cancer-associated fibroblasts with comparable diagnostic performance to 2-[18F]FDG PET/CT for identifying the primary lesions of OSCC. • [68Ga]Ga-FAPI PET/CT showed higher specificity and accuracy for the evaluation of neck lymph node metastases of OSCC than 2-[18F]FDG PET/CT, especially for N0 neck status.

2-[18F]FDG PET/CT parameters associated with WHO/ISUP grade in clear cell renal cell carcinoma.

PURPOSE: To explore the potential parameters from preoperative 2-[18F]FDG PET/CT that might associate with the World Health Organization/the International Society of Urological Pathology (WHO/ISUP) grade in clear cell renal cell carcinoma (ccRCC). METHODS: One hundred twenty-five patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery or biopsy were retrospectively reviewed. The metabolic parameters and imaging features obtained from 2-[18F]FDG PET/CT examinations were analyzed in combination with clinical characteristics. Univariate and multivariate logistic regression analyses were performed to identify the predictive factors of WHO/ISUP grade. RESULTS: Metabolic parameters of primary tumor maximum standardized uptake value (SUVmax), tumor-to-liver SUV ratio (TLR), and tumor-to-kidney SUV ratio (TKR) were significantly different between any two of the four different WHO/ISUP grades, except those between the WHO/ISUP grade 3 and grade 4. The optimal cutoff values to predict high WHO/ISUP grade for SUVmax, TLR, and TKR were 4.15, 1.63, and 1.59, respectively. TLR (AUC: 0.841) was superior to TKR (AUC: 0.810) in distinguishing high and low WHO/ISUP grades (P = 0.0042). In univariate analysis, SUVmax, TLR, TKR, primary tumor size, tumor thrombus, distant metastases, and clinical symptoms could discriminate between the high and low WHO/ISUP grades (P < 0.05). In multivariate analysis, TLR (P < 0.001; OR: 1.732; 95%CI: 1.289-2.328) and tumor thrombus (P < 0.001; OR: 6.199; 95%CI: 2.499-15.375) were significant factors for differentiating WHO/ISUP grades. CONCLUSION: Elevated TLR (> 1.63) and presence of tumor thrombus from preoperative 2-[18F]FDG PET/CT can distinguish high WHO/ISUP grade ccRCC effectively. 2-[18F]FDG PET/CT may be a feasible method for noninvasive assessment of WHO/ISUP grade.

Prognostic Impact of Pretreatment 2-[18F]-FDG PET/CT Parameters in Primary Gastric DLBCL.

Background and Objectives: Primary gastric diffuse large-B cell lymphoma (DLBCL) is an aggressive lymphoma subtype with high 18F-FDG avidity but unclear criteria for 2-[18F]-FDG PET/CT in the evaluation of treatment response and prognostication. Our aim was to investigate whether the pretreatment 2-[18F]-FDG PET/CT variables may predict treatment response (at end of first-line therapy) and prognosis in primary gastric DLBCL. Materials and Methods: we included 57 patients with a diagnosis of primary gastric DLBCL and a baseline 2-[18F]-FDG PET/CT and an end of treatment PET/CT after 6 cycles of R-CHOP chemotherapy. We analyzed PET images qualitatively and semi-quantitatively by deriving the maximum standardized uptake value body weight (SUVbw), the maximum standardized uptake value lean body mass (SUVlbm), the maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume and total lesion glycolysis of gastric lesion (gMTV and gTLG), and total MTV (tMTV) and TLG. Survival curves were plotted according to the Kaplan-Meier analysis. Results: at a median follow up of 80 months, the median PFS and OS were 69 and 80 months. Baseline gMTV, gTLG, tMTV, and TLG were significantly higher in patients with incomplete response (partial response and progression) compared to complete response group. tMTV and TLG were confirmed to be independent prognostic factors both for PFS (p = 0.023 and p = 0.038) and OS (p = 0.038 and p = 0.026); instead, the other metabolic parameters were not related to outcome survival. Conclusions: high tMTV and TLG were significantly correlated with shorter survival (PFS and OS) and may predict incomplete response after therapy.

Classification of Pulmonary Nodules in 2-[18F]FDG PET/CT Images with a 3D Convolutional Neural Network.

Purpose: 2-[18F]FDG PET/CT plays an important role in the management of pulmonary nodules. Convolutional neural networks (CNNs) automatically learn features from images and have the potential to improve the discrimination between malignant and benign pulmonary nodules. The purpose of this study was to develop and validate a CNN model for classification of pulmonary nodules from 2-[18F]FDG PET images. Methods: One hundred thirteen participants were retrospectively selected. One nodule per participant. The 2-[18F]FDG PET images were preprocessed and annotated with the reference standard. The deep learning experiment entailed random data splitting in five sets. A test set was held out for evaluation of the final model. Four-fold cross-validation was performed from the remaining sets for training and evaluating a set of candidate models and for selecting the final model. Models of three types of 3D CNNs architectures were trained from random weight initialization (Stacked 3D CNN, VGG-like and Inception-v2-like models) both in original and augmented datasets. Transfer learning, from ImageNet with ResNet-50, was also used. Results: The final model (Stacked 3D CNN model) obtained an area under the ROC curve of 0.8385 (95% CI: 0.6455-1.0000) in the test set. The model had a sensibility of 80.00%, a specificity of 69.23% and an accuracy of 73.91%, in the test set, for an optimised decision threshold that assigns a higher cost to false negatives. Conclusion: A 3D CNN model was effective at distinguishing benign from malignant pulmonary nodules in 2-[18F]FDG PET images. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-023-00821-6.

Induction of Arterial Inflammation by Immune Checkpoint Inhibitor Therapy in Lung Cancer Patients as Measured by 2-[18F]FDG Positron Emission Tomography/Computed Tomography Depends on Pre-Existing Vascular Inflammation.

BACKGROUND: Immune checkpoint inhibitors (ICI) are one of the most effective therapies in oncology, albeit associated with various immune-related adverse events also affecting the cardiovascular system. METHODS: We aimed to investigate the effect of ICI on arterial 2-[18F]FDG uptake by using 2-[18F]FDG PET/CT imaging pre/post treatment in 47 patients with lung cancer. Maximum 2-[18F]FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along six arterial segments. We classified the arterial PET lesions by pre-existing active inflammation (cut-off: TBRpre ≥ 1.6). 2-[18F]FDG metabolic activity pre/post treatment was also quantified in bone marrow, spleen, and liver. Circulating blood biomarkers were additionally collected at baseline and after immunotherapy. RESULTS: ICI treatment resulted in significantly increased arterial inflammatory activity, detected by increased TBRs, in all arterial PET lesions analyzed. In particular, a significant elevation of arterial 2-[18F]FDG uptake was only recorded in PET lesions without pre-existing inflammation, in calcified as well as in non-calcified lesions. Furthermore, a significant increase in arterial 2-[18F]FDG metabolic activity after immunotherapy was solely observed in patients not previously treated with chemotherapy or radiotherapy as well as in those without CV risk factors. No significant changes were recorded in either 2-[18F]FDG uptake of bone marrow, spleen and liver after treatment, or the blood biomarkers. CONCLUSIONS: ICI induces vascular inflammation in lung cancer patients lacking pre-existing arterial inflammation.

Discordant Molecular Imaging Findings with 2-[18F]FDG and [68Ga]Ga-PSMA PET/CT in a Patient with Both Bladder and Prostate Cancer.

The prevalence of double primary prostate and bladder cancer is not uncommon. Though both share a common pathway of malignant transformation, they bear to differ in the case of 2-[18F]FDG PET/CT and [68Ga]Ga-PSMA uptake. We present a case of double primary cancer involving the bladder and prostate, where the prostatic primary showed intense [68Ga]Ga-PSMA uptake with non-avid skeletal and pulmonary metastases, which showed intense 2-[18F]FDG uptake, thus showing discordance due to different clonal origins.

Metabolic parameters of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography for prognosis in patients with gallbladder adenocarcinoma: a cohort study.

Background: The incidence of gallbladder adenocarcinoma (GBA) is relatively low, yet it exhibits a high degree of malignancy and a significantly low 5-year survival rate. The aim of this study was to investigate the prognostic value of pretreatment 2-[18F]fluoro-D-glucose positron emission tomography {2-[18F]FDG PET} parameters in predicting outcomes for patients with GBA. Methods: In total, 67 patients with GBA who underwent 2-[18F]FDG PET/computed tomography (CT) before treatment were retrospectively analyzed at Chinese PLA General Hospital from January 2012 to June 2022. All patients were diagnosed by pathology, and their baseline characteristics and clinical data were collected. The metabolic PET parameters of the primary and metastatic lesions were measured, including the maximum and average standardized uptake values (SUVs), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The prognostic significance of metabolic parameters and other clinical variables was assessed using Cox proportional hazards regression models. Differences in progression-free survival (PFS) and overall survival (OS) in relation to metabolic parameters were examined using the Kaplan-Meier method. Results: During a median follow-up period of 14.2 months, 43 patients (64.2%) experienced tumor recurrence or progression, and 38 patients (56.7%) died of cancer. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.007), distant metastases (P=0.049), tumor differentiation (P=0.028), surgery (P=0.014), carcinoembryonic antigen (CEA) level (P=0.030), carbohydrate antigen 19-9 (CA19-9) level (P=0.003), TLG (P=0.005), MTV (P<0.001), sum of the TLGs of the primary and metastatic lesions (total TLG, tTLG) (P=0.001), and sum of the MTVs of the primary and metastatic lesions (total MTV, tMTV) (P<0.001) were significant predictors of PFS. In multivariate analysis, MTV was an independent predictor of PFS [hazard ratio (HR) =2.785; 95% confidence interval (CI): 1.204-6.441; P=0.017]. In the univariate Cox regression analysis, liver parenchymal invasion (P=0.001), lymph node metastasis (P=0.027), distant metastases (P=0.036), tumor differentiation (P=0.047), surgery (P=0.002), neutrophil-to-lymphocyte ratio (NLR) (P=0.011), CEA level (P=0.036), CA19-9 level (P<0.001), TLG (P=0.007), MTV (P<0.001), tTLG (P=0.003), and tMTV (P<0.001) were significant predictors of OS. In the multivariate analysis, higher CA19-9 levels >37 U/mL and a greater tMTV (HR =2.961; 95% CI: 1.092-8.024; P=0.033) were predictive of OS. Conclusions: Our study results suggest that pretreatment 2-[18F]FDG PET parameters can not only assist in the diagnosis of patients with GBA but may also serve as predictive factors for the prognosis of these patients and should thus be applied in their treatment.