[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.

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.

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.

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.

18F-fluorocholine PET/CT semi-quantitative analysis in patients affected by primary hyperparathyroidism: a comparison between laboratory and functional data.

INTRODUCTION: This retrospective study aims to establish 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) performance in finding hyperfunctioning parathyroid glands, analyze a potential role for semi-quantitative PET parameters and assess factors that may influence PET/CT outcome. METHODS: Forty patients with suspect primary hyperparathyroidism (pHPT) and negative/equivocal conventional imaging underwent FCH-PET/CT in our Institution. For every lesion, visual and semi-quantitative analyses were performed on PET/CT images. In qualitative analysis, a lesion was considered positive if a clear focus of uptake, significantly higher than normal thyroid tissue, was identifiable. Ectopic focal uptake was also regarded as positive PET result. Lesion SUVMax was measured by assigning a spheric VOI to the suspect area of uptake. Thyroid SUVMean was assessed by placing a spheric VOI inside the contralateral thyroid lobe, and SUVratio was calculated using this background region. All patients were subsequently submitted to surgery and histopathologic workup. Sensitivity, positive predictive value (PPV) and accuracy were calculated based on histopathologic reports for every lesion. Pearson's test was used to assess a correlation between laboratory and histopathologic features with SUVr. RESULTS: Four out of the 40 patients who underwent surgery for pHPT had more than one histologic proven unhealthy parathyroid and three had papillary thyroid cancer (PTC). A total of 48 lesions were analyzed. We found 42/48 lesions (87.5%) to have true-positive uptake, whereas three lesions (6.7%) had false-positive uptake (PTC). Three histologic proven parathyroid adenomas showed no uptake (6.7%); the sensitivity/PPV were 93.3% and accuracy was 87,8%. Pearson's test showed a significant correlation between PTH values and parathyroid size with SUVr values (r = 0.56 and 0.55, respectively, p < 0.01 for both features). DISCUSSION: As stated in recent literature, we observed excellent diagnostic sensitivity of FCH-PET/CT in patients with pHPT, providing surgeons a fine tool to optimize treatment. More studies are needed to improve the evaluability of semi-quantitative parameters towards a further improvement of diagnostic accuracy.

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.

Parkinsonian traits in amyotrophic lateral sclerosis (ALS): a prospective population-based study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by a spectrum of phenotypes, but only a few studies have addressed the presence of parkinsonian (PK) symptoms. The aim of our study was to investigate the occurrence of PK features in a prospective population-based cohort of ALS patients, determining their demographic, clinical, neuropsychological and genetic characteristics, and identifying their morphological and functional imaging correlates. METHODS: A consecutive series of ALS patients were enrolled and prospectively followed for 2 years. Patients were classified according to the presence (ALS-PK) or absence (ALS) of PK signs, and they underwent neuropsychological testing, genetic analysis for the main ALS and PD genes, brain MRI and 18F-FDG-PET. ALS-PK patients underwent 123I-ioflupane SPECT. RESULTS: Out of 114 eligible patients, 101 (64 men; mean age at onset 65.1 years) were recruited. Thirty-one patients (30.7%) were classified as ALS-PK. Compared to ALS patients, ALS-PK patients were more frequently male, but did not differ for any other clinical, demographic or neuropsychological factors. 123I-ioflupane SPECT was normal in all but two ALS-PK patients. At 18F-FDG-PET, ALS-PK patients showed a relative hypometabolism in left cerebellum and a relatively more preserved metabolism in right insula and frontal regions; MRI fractional anisotropy was reduced in the sagittal stratum and increased in the retrolenticular part of the internal capsule. CONCLUSIONS: In our study, about 30% of ALS patients showed PK signs. Neuroimaging data indicate that PK signs are due to the involvement of brain circuitries other than classical nigrostriatal ones, strengthening the hypothesis of ALS as a complex multisystem disease.

Diagnostic and prognostic value of 18F-FDG PET/CT in comparison with morphological imaging in primary adrenal gland malignancies - a multicenter experience.

OBJECTIVE: To evaluate the diagnostic and prognostic role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in comparison to morphological imaging such as computed tomography in primary adrenal malignancies. MATERIALS AND METHODS: In this multicenter retrospective study, 68 patients with adrenal malignancy were included. All patients had histologically proven diagnosis of primary adrenal malignancy (adrenocortical carcinoma, malignant pheochromocytoma, neuroblastoma and lymphoma), one whole body (18)F-FDG PET/CT scan and one whole-body contrast enhancement computed tomography (CECT) scan acquired within one month and were followed clinically and by performing morphological tests for at least 12 months. RESULTS: Overall sensitivity, specificity, accuracy, positive and negative predictive values for CECT and (18)F-FDG PET/CT were respectively, 59%, 100%, 65%, 100%, 27% and 75%, 100%, 82%, 100% and 63%. For adrenocortical carcinomas, (18)F-FDG PET/CT showed a better accuracy (93.4%) than CECT (75%). For neuroblastomas (18)F-FDG PET/CT also showed better accuracy (70.4%) than CECT (66.7%). For malignant pheochromocytomas (18)F-FDG PET/CT and CECT showed the same accuracy (90%). For primary adrenal lymphomas, (18)F-FDG PET/CT showed better accuracy (100%) than CECT (74.41%). Kaplan-Mayer curves showed that "histotypes" and "metastases at the last follow-up" were similarly detected for both disease free survival (DFS) and overall survival (OS), while "global 18F-FDG PET/CT" and "presence of metastases at diagnosis" were significant for DFS. Stratifying the sample by the presence or absence of metastases at diagnosis, standardized uptake value (SUVmax) was a significant prognostic factor for DFS when metastases were absent (Wald test=7.035, P=0.008). CONCLUSION: Our multicenter study demonstrated that (18)F-FDG PET/CT better than CECT diagnosed adrenal malignancies achieving also a good prognostic performance. Therefore management algorithms should include (18)F-FDG PET/CT.

Multicenter Semiquantitative Evaluation of (123)I-FP-CIT Brain SPECT.

AIMS: The aims of this study were: (1) to cross-compare data from semiquantitative, software-assisted, and phantom-corrected evaluations of (123)I-ioflupane [(123)I]N-ω-fluoropropyl-2ß-carbomethoxy-3ß-{4-iodophenyl}nortropane FP-CIT brain single-photon emission computed tomography (SPECT) acquired in three centers; (2) to assess the accuracy of semiquantitative evaluation; and (3) to identify the threshold with the best accuracy, sensitivity, and specificity in patients with suspected Parkinsonian Syndrome. MATERIAL AND METHODS: Two-hundred-twenty patients, acquired in three centers, were included. All of them underwent (123)I-FP-CIT brain SPECT. All examinations were analyzed with the freely available software, BasGan, and semiquantitative data were used to predict disease. Analysis was based on the values from the most deteriorated putamen and caudate, normalized for age, and corrected by anthropomorphic phantom data. Receiver operating characteristic (ROC) analysis was performed and areas under the curve (AUC) were estimated. RESULTS: Analysis showed high AUCs (.880, .866, .920, and .882 for each center and multicenter setting). Best thresholds were 1.53 and 1.56 for putamen and caudate, respectively. Thresholds of putamen data showed sensitivity and specificity of 86% and 89%, respectively, in the multicenter setting. Neither sensibility nor specificity showed significant differences among centers. CONCLUSION: A unique, accurate threshold for all centers, with high sensitivity and specificity was identified. Semiquantitative assessment of (123)I-FP-CIT brain SPECT among different centers resulted reliable, accurate, and potentially useful in clinical trials.