Prostate-Specific Membrane Antigen Positron Emission Tomography Oncological Applications beyond Prostate Cancer in Comparison to Other Radiopharmaceuticals.

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed on the surface of tumor cells in most of the patients affected by prostate adenocarcinoma (PCa). However, PSMA expression has also been demonstrated in the endothelial cells of newly formed vessels of various solid tumors, suggesting a role for PSMA in neoangiogenesis. In this scenario, gallium-68 (68Ga) or fluoro-18 (18F)-labeled PSMA positron emission tomography (PET) may play a role in tumors other than PCa, generally evaluated employing other radiopharmaceuticals targeting different pathways. This review aims to investigate the detection rate of PSMA-PET compared to other radiopharmaceuticals (especially [18F]FDG) in non-prostate tumors to identify patients who may benefit from the use of such a theragnostic agent. METHODS: We performed a bibliographic search on three different databases until February 2024 using the following terms: "positron emission tomography", "PET", "PET/CT", "Prostate-specific membrane antigen", "PSMA", "non-prostate", "not prostate cancer", "solid tumor", "FDG", "Fluorodeoxyglucose", "FAPi", "FET", "MET", "DOPA", "choline", "FCH", "FES", "DOTATOC", "DOTANOC", and "DOTATATE". Only original articles edited in English with at least 10 patients were included. RESULTS: Out of a total of 120 articles, only 25 original articles comparing PSMA with other radiotracers were included in this study. The main evidence was demonstrated in renal cell carcinoma, where PSMA showed a higher detection rate compared to [18F]FDG PET/CT, with implications for patient management. PSMA PET may also improve the assessment of other entities, such as gliomas, in defining regions of early neoangiogenesis. Further data are needed to evaluate the potential role of PSMA-PET in triple-negative breast cancer as a novel therapeutic vascular target. Finally, unclear applications of PSMA-PET include thyroid and gastrointestinal tumors. CONCLUSIONS: The present review shows the potential use of PSMA-labeled PET/CT in solid tumors beyond PCa, underlining its value over other radiopharmaceuticals (mainly [18F]FDG). Prospective clinical trials with larger sample sizes are crucial to further investigate these possible clinical applications.

[11C]Choline PET/CT in a Patient with Prostate Cancer Biochemical Recurrence Showing Two Suspicious Findings in the Breast and Liver.

A 79-year-old man with prostate cancer (PCa) was referred to our center to perform a [11C]Choline PET/CT for biochemical recurrence. Positron emission tomography/computed tomography (PET/CT) scan detected PCa recurrence in the prostate gland and several pelvic and abdominal lymph nodes. Two abnormal uptakes were also identified in the right breast and in the liver, respectively. Breast histological findings turned out to be gynecomastia, while the liver lesion resulted in a benign perfusion anomaly at follow-up magnetic resonance imaging (MRI). Although incidental findings were benign in this case, it is important to always investigate abnormal uptakes of [11C]Choline, as it could be an expression of further metastases or synchronous malignancies such as breast cancer and hepatocellular carcinoma.

Applications of Artificial Intelligence and Radiomics in Molecular Hybrid Imaging and Theragnostics for Neuro-Endocrine Neoplasms (NENs).

Nuclear medicine has acquired a crucial role in the management of patients with neuroendocrine neoplasms (NENs) by improving the accuracy of diagnosis and staging as well as their risk stratification and personalized therapies, including radioligand therapies (RLT). Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both diagnostic and therapeutic settings by improving the prediction of the tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art AI and radiomics applications in the molecular imaging of NENs.

PET Radiomics and Response to Immunotherapy in Lung Cancer: A Systematic Review of the Literature.

The aim of this review is to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET) radiomics in lung cancer patient candidates or those undergoing immunotherapy. MATERIALS AND METHODS: A systematic review was conducted on databases and web sources. English-language original articles were considered. The title and abstract were independently reviewed to evaluate study inclusion. Duplicate, out-of-topic, and review papers, or editorials, articles, and letters to editors were excluded. For each study, the radiomics analysis was assessed based on the radiomics quality score (RQS 2.0). The review was registered on the PROSPERO database with the number CRD42023402302. RESULTS: Fifteen papers were included, thirteen were qualified as using conventional radiomics approaches, and two used deep learning radiomics. The content of each study was different; indeed, seven papers investigated the potential ability of radiomics to predict PD-L1 expression and tumor microenvironment before starting immunotherapy. Moreover, two evaluated the prediction of response, and four investigated the utility of radiomics to predict the response to immunotherapy. Finally, two papers investigated the prediction of adverse events due to immunotherapy. CONCLUSIONS: Radiomics is promising for the evaluation of TME and for the prediction of response to immunotherapy, but some limitations should be overcome.

Can Baseline [18F]FDG PET/CT Predict Response to Immunotherapy After 6 Months and Overall Survival in Patients with Lung Cancer or Malignant Melanoma? A Multicenter Retrospective Study.

Aim: To assess the role of baseline 18F-fluorodeoxyglucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in predicting response to immunotherapy after 6 months and overall survival (OS) in patients with lung cancer (LC) or malignant melanoma (MM). Materials and Methods: Data from a multicenter, retrospective study conducted between March and November 2021 were analyzed. Patients >18 years old with a confirmed diagnosis of LC or MM, who underwent a baseline [18F]FDG-PET/CT within 1-2 months before starting immunotherapy and had a follow-up of at least 12 months were included. PET scans were examined visually and semiquantitatively by physicians at peripheral centers. The metabolic tumor burden (number of lesions with [18F]FDG-uptake) and other parameters were recorded. Clinical response was assessed at 3 and 6 months after starting immunotherapy, and OS was calculated as the time elapsing between the PET scan and death or latest follow-up. Results: The study concerned 177 patients with LC and 101 with MM. Baseline PET/CT was positive in primary or local recurrent lesions in 78.5% and 9.9% of cases, in local/distant lymph nodes in 71.8% and 36.6%, in distant metastases in 58.8% and 84%, respectively, in LC and in MM patients. Among patients with LC, [18F]FDG-uptake in primary/recurrent lung lesions was more often associated with no clinical response to immunotherapy after 6 months than in cases without any tracer uptake. After a mean 21 months, 46.5% of patients with LC and 37.1% with MM had died. A significant correlation emerged between the site/number of [18F]FDG foci and death among patients with LC, but not among those with MM. Conclusions: In patients with LC who are candidates for immunotherapy, baseline [18F]FDG-PET/CT can help to predict response to this therapy after 6 months, and to identify those with a poor prognosis based on their metabolic parameters. For patients with MM, there was only a weak correlation between baseline PET/CT parameters, response to therapy, and survival.

The Role of Theragnostics in Breast Cancer: A Systematic Review of the Last 12 Years.

BACKGROUND: Breast cancer is the most common malignancy in women, with high morbidity and mortality. Molecular alterations in breast cancer involve the expression or upregulation of various molecular targets that can be used for diagnostic nuclear medicine imaging and radiopharmaceutical treatment. Theragnostics is based on the binding of radionuclides to molecular targets. These radionuclides can induce a cytotoxic effect on the specific tumor cell (target) or its vicinity, thus allowing a personalized approach to patients with effective treatment and comparably small side effects. AIM: This review aims to describe the most promising molecular targets currently under investigation for theragnostics and precision oncology in breast cancer. METHODS: A comprehensive literature search of studies on theragnostics in breast cancer was performed in the PubMed, PMC, Scopus, Google Scholar, Embase, Web of Science, and Cochrane library databases, between 2010 and 2022, using the following terms: breast neoplasm*, breast, breast cancer*, theragnostic*, theranostic*, radioligand therap*, RLT, MET, FLT, FMISO, FES, estradiol, trastuzumab, PD-L1, PSMA, FAPI, FACBC, fluciclovine, FAZA, GRPR, DOTATOC, DOTATATE, CXC4, endoglin, gastrin, mucin1, and syndecan1. RESULTS: Fifty-three studies were included in the systematic review and summarized in six clinical sections: 1) human epidermal growth factor receptor 2 (HER2); 2) somatostatin receptors (SSTRS); 3) prostate-specific membrane antigen radiotracers (PSMA); 4) fibroblast activation protein-α targeted radiotracers; 5) gastrin-releasing peptide receptor-targeted radiotracers; 6) other radiotracers for theragnostics. CONCLUSION: The theragnostic approach will progressively allow better patient selection, and improve the prediction of response and toxicity, avoiding unnecessary and costly treatment.

ITA-IMMUNO-PET: The Role of [18F]FDG PET/CT for Assessing Response to Immunotherapy in Patients with Some Solid Tumors.

AIM: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. METHODS: Data recorded in a multicenter (n = 17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial [18F]FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET scans, and both the obtained responses were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31-89 years) in all. The most common neoplasm was lung cancer (56.9%), followed by malignant melanoma (32.5%). Nivolumab was administered in 46.3%, and pembrolizumab in 40.5% of patients. Baseline PET and a first PET scan performed at a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. After a median 18 (1-137) months, 113 (36.3%) patients had died. On Kaplan-Meier analysis, metabolic responders on the first two serial PET scans showed a better prognosis than non-responders, while clinical response became prognostically informative from the second assessment after starting immunotherapy onwards. CONCLUSIONS: [18F]FDG PET/CT could have a role in the assessment of response to immunotherapy in patients with some solid tumors. It can provide prognostic information and thus contribute to a patient's appropriate treatment. Prospective randomized controlled trials are mandatory.

Prediction of benzimidazole therapy duration with PET/CT in inoperable patients with alveolar echinococcosis.

Alveolar echinococcosis is a rare parasitic disease, most frequently affecting the liver, as a slow-growing tumor-like lesion. If inoperable, long-term benzimidazole therapy is required, which is associated with high healthcare costs and occasionally with increased morbidity. The aim of our study was to determine the role 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in staging of patients with alveolar echinococcosis and to identify quantitative imaging parameters related to patient outcome and/or duration of benzimidazole therapy. In this single-center retrospective cohort study, 47 PET/CT performed for staging in patients with confirmed alveolar echinococcosis were analysed. In 43 patients (91%) benzimidazole therapy was initiated and was successfully stopped after a median of 870 days (766-2517) in 14/43 patients (33%). In inoperable patients, tests for trend of survivor functions displayed clear trends for longer benzimidazole therapy duration (p = 0.05; n = 25), and for longer time intervals to reach non-detectable serum concentration of Em-18 antibodies (p = 0.01, n = 15) across tertiles of SUVratio (maximum standardized uptake value in the echinococcus manifestation compared to normal liver tissue). Hence, in inoperable patients with alveolar echinococcosis, PET/CT performed for staging may predict the duration of benzimidazole therapy.

Radiomics and artificial intelligence in prostate cancer: new tools for molecular hybrid imaging and theragnostics.

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer.

Non-conventional and Investigational PET Radiotracers for Breast Cancer: A Systematic Review.

Breast cancer is one of the most common malignancies in women, with high morbidity and mortality rates. In breast cancer, the use of novel radiopharmaceuticals in nuclear medicine can improve the accuracy of diagnosis and staging, refine surveillance strategies and accuracy in choosing personalized treatment approaches, including radioligand therapy. Nuclear medicine thus shows great promise for improving the quality of life of breast cancer patients by allowing non-invasive assessment of the diverse and complex biological processes underlying the development of breast cancer and its evolution under therapy. This review aims to describe molecular probes currently in clinical use as well as those under investigation holding great promise for personalized medicine and precision oncology in breast cancer.

Event-free survival after 68 Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC) patients eligible for salvage therapy.

BACKGROUND/AIM: Prostate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. MATERIALS AND METHODS: This analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy. RESULTS: One-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43-1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5-40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53-1.28] vs 0.51 [IQR: 0.36-0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7-11.6] vs 12.7 [IQR: 6.6-24.3] months) (p < 0.001) compared to event-free patients. The Kaplan-Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001). CONCLUSION: Low PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

BSREM for Brain Metastasis Detection with 18F-FDG-PET/CT in Lung Cancer Patients.

The aim of the study was to analyze the use of block sequential regularized expectation maximization (BSREM) with different ß-values for the detection of brain metastases in digital fluorine-18 labeled 2-deoxy-2-fluoro-D-glucose (18F-FDG) PET/CT in lung cancer patients. We retrospectively analyzed staging/restaging 18F-FDG PET/CT scans of 40 consecutive lung cancer patients with new brain metastases, confirmed by MRI. PET images were reconstructed using BSREM (ß-values of 100, 200, 300, 400, 500, 600, 700) and OSEM. Two independent blinded readers (R1 and R2) evaluated each reconstruction using a 4-point scale for general image quality, noise, and lesion detectability. SUVmax of metastases, brain background, target-to-background ratio (TBR), and contrast recovery (CR) ratio were recorded for each reconstruction. Among all reconstruction techniques, differences in qualitative parameters were analyzed using non-parametric Friedman test, while differences in quantitative parameters were compared using analysis of variances for repeated measures. Cohen's kappa (k) was used to measure inter-reader agreement. The overall detectability of brain metastases was highest for BSREM200 (R1: 2.83 ± 1.17; R2: 2.68 ± 1.32) and BSREM300 (R1: 2.78 ± 1.23; R2: 2.68 ± 1.36), followed by BSREM100, which had lower accuracy owing to noise. The highest median TBR was found for BSREM100 (R1: 2.19 ± 1.05; R2: 2.42 ± 1.08), followed by BSREM200 and BSREM300. Image quality ratings were significantly different among reconstructions (p < 0.001). The median quality score was higher for BSREM100-300, and both noise and metastases' SUVmax decreased with increasing ß-value. Inter-reader agreement was particularly high for the detectability of photopenic metastases and blurring (all k > 0.65). BSREM200 and BSREM300 yielded the best results for the detection of brain metastases, surpassing both BSREM400 and OSEM, typically used in clinical practice.

[68Ga]DOTATOC PET/CT Radiomics to Predict the Response in GEP-NETs Undergoing [177Lu]DOTATOC PRRT: The "Theragnomics" Concept.

Despite impressive results, almost 30% of NET do not respond to PRRT and no well-established criteria are suitable to predict response. Therefore, we assessed the predictive value of radiomics [68Ga]DOTATOC PET/CT images pre-PRRT in metastatic GEP NET. We retrospectively analyzed the predictive value of radiomics in 324 SSTR-2-positive lesions from 38 metastatic GEP-NET patients (nine G1, 27 G2, and two G3) who underwent restaging [68Ga]DOTATOC PET/CT before complete PRRT with [177Lu]DOTATOC. Clinical, laboratory, and radiological follow-up data were collected for at least six months after the last cycle. Through LifeX, we extracted 65 PET features for each lesion. Grading, PRRT number of cycles, and cumulative activity, pre- and post-PRRT CgA values were also considered as additional clinical features. [68Ga]DOTATOC PET/CT follow-up with the same scanner for each patient determined the disease status (progression vs. response in terms of stability/reduction/disappearance) for each lesion. All features (PET and clinical) were also correlated with follow-up data in a per-site analysis (liver, lymph nodes, and bone), and for features significantly associated with response, the Δradiomics for each lesion was assessed on follow-up [68Ga]DOTATOC PET/CT performed until nine months post-PRRT. A statistical system based on the point-biserial correlation and logistic regression analysis was used for the reduction and selection of the features. Discriminant analysis was used, instead, to obtain the predictive model using the k-fold strategy to split data into training and validation sets. From the reduction and selection process, HISTO_Skewness and HISTO_Kurtosis were able to predict response with an area under the receiver operating characteristics curve (AUC ROC), sensitivity, and specificity of 0.745, 80.6%, 67.2% and 0.722, 61.2%, 75.9%, respectively. Moreover, a combination of three features (HISTO_Skewness; HISTO_Kurtosis, and Grading) did not improve the AUC significantly with 0.744. SUVmax, however, could not predict the response to PRRT (p = 0.49, AUC 0.523). The presented preliminary "theragnomics" model proved to be superior to conventional quantitative parameters to predict the response of GEP-NET lesions in patients treated with complete [177Lu]DOTATOC PRRT, regardless of the lesion site.

Histopathological Features of Parathyroid Adenoma and 18F-Choline Uptake in PET/MR of Primary Hyperparathyroidism.

BACKGROUND: The aim of this study was to assess the relationship between the histopathological properties of hyperfunctioning parathyroids and parathyroid 18F-choline uptake. PATIENTS AND METHODS: A total of 31 parathyroid adenomas were retrospectively analyzed in patients with primary hyperparathyroidism and preoperative 18F-choline PET/MR. PET/MR parameters of parathyroid glands (SUVmax and target-to-background ratio in early-phase [EP] and late-phase [LP]), MRI volume, preoperative parathyroid hormone (PTH) serum concentration, and postoperative histopathology (predominant cell type and growth pattern of adenoma cells, location and size of adenoma) were assessed. The relationship of PET/MR parameters, PTH, and histological parameters was determined using linear regression, Spearman correlation and Kruskal-Wallis test. RESULTS: The median volume of parathyroid adenoma was 421.78 ± 142.46 mm3 (46.39-4412.69). Adenomas were predominantly composed of chief, water-clear, and oncocytic/oxyphilic cells in 27/31, 2/31, and 2/31 cases, respectively. The growth pattern was predominantly solid, follicular, and trabecular in 18/31, 8/31, and 5/31, respectively. The SUVmax was 6.71 ± 3.39 in EP and 6.91 ± 3.97 in LP. Follicular growth pattern had slightly higher EP SUVmax (trabecular: 4.12 ± 0.56; solid: 6.62 ± 3.19; follicular: 8.56 ± 3.96; P = 0.046). Spearman correlation showed strong positive correlation between volume and both EP and LP SUVmax (0.626; P = 0.0001 and 0.576; P = 0.0001, respectively). Linear regression analysis revealed significant correlation between PTH level and EP and LP SUVmax (both P = 0.001); in contrast, no correlation was found between PTH level and both cell type and growth pattern. CONCLUSIONS: Our findings suggest that 18F-choline uptake of parathyroid adenomas might be associated both with the histological growth pattern and adenoma volume, but not with a specific cell type.

Prognostic Value of Whole-Body PET Volumetric Parameters Extracted from 68Ga-DOTATOC PET/CT in Well-Differentiated Neuroendocrine Tumors.

Our objective was to evaluate the prognostic value of somatostatin receptor tumor burden on 68Ga-DOTATOC PET/CT in patients with well-differentiated (WD) neuroendocrine tumors (NETs). Methods: We retrospectively analyzed the 68Ga-DOTATOC PET/CT scans of 84 patients with histologically confirmed WD NETs (51 grade 1, 30 grade 2, and 3 grade 3). For each PET/CT scan, all 68Ga-DOTATOC-avid lesions were independently segmented by 2 operators using a customized threshold based on the healthy liver SUVmax (LIFEx, version 5.1). Somatostatin receptor-expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE = SRETV × SUVmean) were extracted for each lesion, and then whole-body SRETV and TLSRE (SRETVwb and TLSREwb, respectively) were defined as the sum of SRETV and TLSRE, respectively, for all segmented lesions in each patient. Time to progression (TTP) was defined as the combination of disease-free survival in patients undergoing curative surgery (n = 10) and progression-free survival for patients with unresectable or metastatic disease (n = 74). TTP and overall survival were calculated by Kaplan-Meier analysis, log-rank testing, and the Cox proportional-hazards regression model. Results: After a median follow-up of 15.5 mo, disease progression was confirmed in 35 patients (41.7%) and 14 patients died. A higher SRETVwb (>39.1 cm3) and TLSREwb (>306.8 g) correlated significantly with a shorter median TTP (12 mo vs. not reached; P < 0.001). In multivariate analysis, SRETVwb (P = 0.005) was the only independent predictor of TTP regardless of histopathologic grade and TNM staging. Conclusion: According to our results, SRETVwb and TLSREwb extracted from 68Ga-DOTATOC PET/CT could predict TTP or overall survival and might have important clinical utility in the management of patients with WD NETs.

Predictive Value of Baseline [18F]FDG PET/CT for Response to Systemic Therapy in Patients with Advanced Melanoma.

BACKGROUND/AIM: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. MATERIALS AND METHODS: Forty four melanoma patients, who underwent [18F]FDG-PET/CT before first-line target therapy (28/44) or immunotherapy (16/44), were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared using the Mann-Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan-Meier analysis. RESULTS: Median (IQR) MTVwb and TLGwb were 13.1 mL and 72.4, respectively. Non-responder patients were 38/44, 26/28 and 12/16 at early evaluation, and 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target, and immunotherapy subgroup, respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p < 0.037) in the whole-cohort and target subgroup and MTVwb and TLGwb (all p < 0.022) in target subgroup. No significant differences were found for the immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversially, MTVlfn, TLGlfn, MTVsoft + lfn, TLGsoft + lfn, MTVwb and TLGwb were significantly associated (all p < 0.05) with OS in both the whole-cohort and target therapy subgroup. CONCLUSIONS: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS.

NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to In Vivo Images.

Lung cancer remains the leading cause of cancer-related death, and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the tumor immune microenvironment (TME). While the response in molecular targeted therapies relies on the presence of specific genetic alterations in tumor cells, accurate ICI biomarkers of response are lacking, and clinical outcome likely depends on multiple factors that are both host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in vitro/ex vivo analysis (ranging from conventional pathology to molecular biology) and in vivo analysis, where molecular imaging is showing an exponential growth and use due to technological advancements and to the new bioinformatics approaches applied to image analyses that allow the recovery of specific features in specific tumor subclones.

Clinical evaluation of data-driven respiratory gating for PET/CT in an oncological cohort of 149 patients: impact on image quality and patient management.

OBJECTIVES: To evaluate the impact of fully automatic motion correction by data-driven respiratory gating (DDG) on positron emission tomography (PET) image quality, lesion detection and patient management. MATERIALS AND METHODS: A total of 149 patients undergoing PET/CT for cancer (re-)staging were retrospectively included. Patients underwent a PET/CT on a digital detector scanner and for every patient a PET data set where DDG was enabled (PETDDG) and as well as where DDG was not enabled (PETnonDDG) was reconstructed. All PET data sets were evaluated by two readers which rated the general image quality, motion effects and organ contours. Further, both readers reviewed all scans on a case-by-case basis and evaluated the impact of PETDDG on additional apparent lesion, change of report, and change of management. RESULTS: In 85% (n = 126) of the patients, at least one bed position was acquired using DDG, resulting in mean scan time increase of 4:37 min per patient in the whole study cohort (n = 149). General image quality was not rated differently for PETnonDDG and PETDDG images (p = 1.000) while motion effects (i.e. indicating general blurring) was rated significantly lower in PETDDG images and organ contours, including liver and spleen, were rated significantly sharper using PETDDG as compared to PETnonDDG (all p < 0.001). In 27% of patients, PETDDG resulted in a change of the report and in a total of 12 cases (8%), PETDDG resulted in a change of further clinical management. CONCLUSION: Deviceless DDG provided reliable fully automatic motion correction in clinical routine and increased lesion detectability and changed management in a considerable number of patients. ADVANCES IN KNOWLEDGE: DDG enables PET/CT with respiratory gating to be used routinely in clinical practice without external gating equipment needed.

COVID-19 and Aspiration Pneumonia: Similar Pulmonary Findings with Different Diagnoses-a Pitfall in [18F]FDG PET/CT.

Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide pandemic. Especially in the centers most affected by the pandemic, symptoms (such as fever, cough, myalgia, or fatigue) and/or radiological signs (such as ground-glass opacity) typically related to COVID-19 often diverted clinicians' attention from other diseases. Despite the urgency to recognize and cure SARS-CoV-2 infection, a plethora of differential diagnoses must be considered, and other diseases must be equally and promptly treated, as described in this case report.

Diagnostic Value of Conventional PET Parameters and Radiomic Features Extracted from 18F-FDG-PET/CT for Histologic Subtype Classification and Characterization of Lung Neuroendocrine Neoplasms.

AIM: To evaluate if conventional Positron emission tomography (PET) parameters and radiomic features (RFs) extracted by 18F-FDG-PET/CT can differentiate among different histological subtypes of lung neuroendocrine neoplasms (Lu-NENs). METHODS: Forty-four naïve-treatment patients on whom 18F-FDG-PET/CT was performed for histologically confirmed Lu-NEN (n = 46) were retrospectively included. Manual segmentation was performed by two operators allowing for extraction of four conventional PET parameters (SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) and 41 RFs. Lu-NENs were classified into two groups: lung neuroendocrine tumors (Lu-NETs) vs. lung neuroendocrine carcinomas (Lu-NECs). Lu-NETs were classified according to histological subtypes (typical (TC)/atypical carcinoid (AC)), Ki67-level, and TNM staging. The least absolute shrink age and selection operator (LASSO) method was used to select the most predictive RFs for classification and Pearson correlation analysis was performed between conventional PET parameters and selected RFs. RESULTS: PET parameters, in particular, SUVmax (area under the curve (AUC) = 0.91; cut-off = 5.16) were higher in Lu-NECs vs. Lu-NETs (p < 0.001). Among RFs, HISTO_Entropy_log10 was the most predictive (AUC = 0.90), but correlated with SUVmax/SUVmean (r = 0.95/r = 0.94, respectively). No statistical differences were found between conventional PET parameters and RFs (p > 0.05) and TC vs. AC classification. Conventional PET parameters were correlated with N+ status in Lu-NETs. CONCLUSION: In our study, conventional PET parameters were able to distinguish Lu-NECs from Lu-NETs, but not TC from AC. RFs did not provide additional information.