Atypical Presentation of Splenic Tissue Mimicking Neuroendocrine Tumor Relapse.

ABSTRACT: A 61-year-old man underwent splenopancreasectomy for a 3-cm neuroendocrine tumor of the body of the pancreas (G2, pT1 pN0, Ki67 3%). Five months after surgery 68Ga-DOTATOC PET/CT showed increased radiotracer uptake in a solid tissue of the splenic fossa, possibly referring to a splenosis nodule. After 19 months, a further 68Ga-DOTATOC PET/CT showed a significant functional and dimensional increase of the previously detected tissue and the appearance of a new finding in the left lateral abdominal wall. In the suspicion of neuroendocrine tumor relapse, the patient underwent surgical excision of the documented lesions. Histology showed splenosis in both nodules.

The Role of Fibroblast Activation Protein Inhibitor Positron Emission Tomography in Inflammatory and Infectious Diseases: An Updated Systematic Review.

The role of fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) is emerging for the assessment of non-oncological diseases, such as inflammatory and infectious diseases, even if the evidence in the literature is still in its initial phases. We conducted a systematic search of Scopus, PubMed/MEDLINE, Embase, and Cochrane library databases for studies published before 31 December 2023 reporting infectious and inflammatory disease imaging with FAPI PET/CT. We included twenty-one studies for a total of 1046 patients. The most frequent disease studied was lung interstitial disease, investigated in six studies for a total of 200 patients, followed by bone and joint diseases in two studies and 185 patients, IgG4-related disease in 53 patients, and Crohn's disease in 30 patients. Despite the heterogeneity of studies in terms of study design and technical features, FAPI PET/CT showed a high detection rate and diagnostic role. Moreover, when compared with 2-[18F]FDG PET/CT (n = 7 studies), FAPI PET/CT seems to have better diagnostic performances. The presence of chronic inflammation and tissue remodeling, typical of immune-mediated inflammatory conditions, may be the underlying mechanism of FAPI uptake.

Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications.

This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head-neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head-neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs.

Breast Relapse of Pediatric B-Cell Acute Lymphoblastic Leukemia After CAR-T Therapy Detected by 18F-FDG PET/CT.

BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. Medullary and extramedullary disease relapse is a well-known occurrence in B-ALL pediatric patients treated with standard chemo-immunotherapy and, more recently, with chimeric antigen receptor (CAR)-T cell therapy. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) emerges as a sensitive imaging tool for detecting disease relapse at extra-medullary sites, with only limited literature evidence in the CAR-T therapy setting. CASE REPORT: In a 12-year-old female treated with CAR-T therapy for B-ALL relapse, 18F-FDG PET/CT scan performed for surveillance, after disease remission, detected a solitary and clinically occult relapse in the breast parenchyma that was histologically confirmed. CONCLUSION: At our knowledge, this is the first report about a pediatric B-ALL patient with a solitary and occult breast relapse after CAR-T therapy, early discovered by 18F-FDG PET/CT during disease monitoring.

Predicting time to treatment in follicular lymphoma on watchful waiting using baseline metabolic tumour burden.

PURPOSE: Asymptomatic patients with follicular lymphoma (FL) and a low tumour burden can be followed without initial therapy, a strategy called watchful waiting (WW). Prediction of the time to treatment (TTT) is still a challenge. We investigated the prognostic value of baseline total metabolic tumour volume (TMTV) and whole-body total lesion glycolysis (WB-TLG) to predict TTT in patients with FL on WW. METHODS: We conducted a retrospective study of 54 patients with FL (grade 1-3a) diagnosed between June 2013 and December 2019, staged with FDG PET/CT, and managed on WW. Median age was 62 years (range 34-85), stage was advanced (III-IV) in 57%, and FLIPI score was intermediate to high (≥ 2) in 52% of the patients. RESULTS: The median TMTV and WB-TLG were 7.1 and 43.3, respectively. With a median follow-up of 59 months, 41% of patients started immuno-chemotherapy. The optimal cut-points to identify patients with TTT within 24 months were 14 for TMTV (AUC 0.70; 95% CI 51-88) and 64 for WB-TLG (AUC 0.71; 95% CI 52-89) (p < 0.005). The probability of not having started treatment within 24 months was 87% for TMTV < 14 and 53% for TMTV ≥ 14 (p < 0.005). TMTV was independent of the FLIPI score for TTT prediction. Patients with both FLIPI ≥ 2 and TMTV ≥ 14 had only an 18% probability of not having started treatment at 36 months, while this probability was 75% in patients with TMTV < 14. CONCLUSION: Metabolic tumour volume parameters may add information to clinical scores to better predict TTT and better stratify patients for interventional studies.

The role of PET/CT in connective tissue disorders: systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus.

Advanced imaging techniques are needed to help clinicians in the diagnosis, in the choice of the right time for therapeutic interventions or for modifications and monitoring of treatment response in patients with autoimmune connective tissue diseases. Nuclear medicine imaging, especially PET/CT and PET/MRI, may play an important role in detecting disease activity, assessing early treatment response as well as in clarifying the complex mechanisms underlying systemic sclerosis, Sjögren's syndrome or systemic lupus erythematosus. In addition, [18F]FDG PET/CT may help in excluding or detecting coexisting malignancies. Other more specific radiopharmaceuticals are being developed and investigated, targeting specific cells and molecules involved in connective tissue diseases. Further larger studies with standardized imaging protocol and image interpretation are strongly required before including PET/CT in the diagnostic work-up of subsets of patients with autoimmune connective tissue diseases.

The impact of the COVID-19 pandemic on oncological disease extent at FDG PET/CT staging: the ONCOVIPET study.

PURPOSE: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at FDG PET/CT staging as surrogate marker. METHODS: Retrospective observational study including cancer patients submitted to FDG PET/CT staging from June 1 to October 31, 2020, and June 1 to October 31, 2019, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, and presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. RESULTS: Six hundred eleven patients were included (240 in 2019 vs 371 in 2020, respectively). A significant increase of advanced disease patients (rate 1.56, P < 0.001), N + or M + patients (rate 1.84 and 2.09, respectively, P < 0.001), and patients with a greater number of involved N stations or M (rate 2.01 and 2.06, respectively, P < 0.001) were found in 2020 compared with data of 2019. Analysis by tumour type showed a significant increase of advanced disease in lymphoma and lung cancer in 2020 compared with 2019 (P < 0.001). In addition, a significant increase of nodal involvement was found in lung, gastro-intestinal, and breast cancers, as well as in lymphoma patients (P < 0.02). A significant increase of distant metastases was found in lung cancers (P = 0.002). CONCLUSION: Cancer patients with advanced disease at FDG PET/CT staging increased in 2020 compared with 2019, following the national lockdown due to the COVID-19 pandemic, 1.5-fold with a significant increase of patients with N or M involvement. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome.

Cavernous Hemangioma: A Potential Pitfall at Delayed 18F-FDG PET/CT Scan.

ABSTRACT: We report the case of a 72-year-old woman who underwent neoadjuvant chemotherapy, right quadrantectomy (invasive ductal carcinoma, G3, pT2pN1pMx), and adjuvant radiotherapy. Two years later, a follow-up CT revealed a hepatic nodule of approximately 1 cm suspected for metastasis. 18F-FDG PET/CT was performed for restaging. Standard total-body 18F-FDG PET/CT acquisition showed no abnormal 18F-FDG uptake in the hepatic nodule. A delayed 18F-FDG PET/CT acquisition of upper abdomen was performed at 180 minutes postradiopharmaceutical injection and showed increased 18F-FDG uptake in the hepatic nodule. After nodule resection, the histological examination proved a cavernous hemangioma.

Incidental Finding of an Ovarian Carcinoid on 11C-Methionine PET/CT.

A 68-year-old woman with a history of multiple myeloma on regular hematological follow-up and with no previous relevant gynecological diseases was found to have an incidental focal uptake by the right ovary at C-methionine PET/CT (C-MET). Transvaginal ultrasound was then performed showing a 2-cm solid right ovarian mass with irregular borders and moderate vascularization at color Doppler examination. Therefore, the patient underwent bilateral salpingectomy, and the final histological results revealed a rare presentation of mature teratoma with insular carcinoid tumor arising from the right ovary.

The prognostic role of FDG PET/CT before combined radio-chemotherapy in anal cancer patients.

OBJECTIVE: We assessed the prognostic value of several FDG PET/CT parameters, measured within the primary tumor and the involved lymph nodes, before definitive radio-chemotherapy (RCT) in anal cancer patients. METHODS: Anal cancer patients with positive baseline FDG PET/CT who underwent definitive RCT from May 2011 to February 2018 were retrospectively assessed. Primary tumour (T)-SUVmax, T-SUVpeak, T-SUVmean, T-MTV, T-TLG, whole-body (WB) MTV, and WB-TLG were measured. Kaplan-Meier curves, Cox-regression analysis, and logistic regression machine-learning technique were used to test for associations between clinical data, metabolic parameters, and outcomes as overall survival (OS), disease-specific survival (DSS), metastatic-free survival (MFS), disease-free survival (DFS), local relapse-free survival (LRFS), and colostomy-free survival (CFS). RESULTS: Fifty-nine patients were included in the study. Median follow-up was 28 months. Higher pre-treatment WB-MTV, T-TLG, and WB-TLG were associated with worse OS (p = 0.025, 0.021, and 0.02, respectively). PET parameters resulted also statistically significant for DSS, DFS, and CFS (p = 0.032, 0.043, 9 × 10-4 for WB-TLG). Cox analysis showed that PET parameters are significant predictors of OS, DSS, DFS, CFS, and LRFS. On multivariate analysis, age, stage, T-SUVpeak, WB-MTV, and T-TLG resulted significantly related to OS. A further stratification for patients with advanced stage (cT3-4 any N or any cT, N + ) showed that MTV and TLG, measured within the primary tumor and the involved nodes, are significantly higher in patients with a worse prognosis. In this subgroup, cut-off values of T- and WB-TLG as well as T- and WB-MTV showed a statistically significant correlation with clinical outcomes. CONCLUSIONS: Pre-treatment metabolic parameters measured within the primary tumor and the involved nodes may represent additional new biomarkers for estimating prognosis in anal cancer patients, especially in advanced stage patients.

68Ga-DOTATOC PET/CT in Thyroid Metastases of Lung Carcinoid.

We report the case of a 43-year-old man with a history of lung carcinoid and a recent detection of thyroid nodules by ultrasound. The cytological analysis raised the suspicion of medullary thyroid carcinoma; however, calcitonin and carcinoembryonic antigen levels were in reference range. Considering the previous diagnosis of lung carcinoid, the patient underwent whole-body Ga-DOTATOC PET/CT. The images showed focal radiopharmaceutical uptake in both thyroid lobes. After thyroidectomy, the histology and immunohistochemistry (negative for calcitonin and positive for chromogranin A) confirmed the neuroendocrine origin of the thyroid nodules, possibly referable to previous lung carcinoid.

Are the simplified methods to estimate Ki in 18F-FDG PET studies feasible in clinical routine? Comparison between three simplified methods.

BACKGROUND: The aim of this study was to verify the feasibility, in clinical practice, of three simplified methods (Hunter, Sadato and another one proposed by our group) to calculate Ki and MRglu of 18F-FDG, comparing the results with those derived by the linear regression (LR) method (considered the golden standard), and also with SUV. METHODS: Forty-five patients (32males, mean age 69±9years) with non-small-cell-lung cancer prospectively enrolled, underwent dynamic 18F-FDG PET-CT over the thorax. Ki was estimated as follows: from a static acquisition and performing one venous blood sampling using the Hunter method; multiplying the SUV for the average plasma clearance rate (kP(T)) and for the initial distribution volume (V0bw) without performing any blood sampling using the Sadato method; multiplying the SUV for a factor F (which encompasses the mean value of haematocrit and plasma volume, both according to patient's sex) without performing any blood sample using ours method. Wilcoxon signed rank and coefficient of determination (R2) were used for statistical analysis. RESULTS: No significant difference was observed between the Ki and MRglu estimated by all three simplified methods and the Ki and MRglu estimated by LR. The highest P values and the lower values of mean differences were observed with our method compared with LR: Ki=0.0392±0.0178 min-1 vs. Ki=0.0392±0.0202 min-1 (P=0.897, MD=0.0001 min-1), respectively; MRglu= 4.47±2.23 ml/min/100g vs. MRglu= 4.43±2.38 ml/min/100g (P=0.839, MD= -0.0373 mL/min/100g), respectively. The highest correlation was observed between the Ki estimated by both Hunter and our methods and the Ki estimated by LR: R2=0.87, R2=0.86, respectively. A good correlation (R2=0.83) was observed between SUV and Ki estimated by LR. CONCLUSIONS: These three simplified methods represent a valid alternative to the more invasive and complex full kinetic analysis. Their "pros" are: the non-invasiveness, the feasibility, the good correlation with the golden standard; their "cons" is that full kinetic analysis provides highest accuracy in Ki determination. Therefore, in clinical oncology routine, the nuclear physicians can choose among different simplified methods especially for monitoring the response to treatment, for tumour grading, and for prognostic stratification, letting the full kinetic analysis to specific centre/studies.

Multifunctional Assessment of Non-Small Cell Lung Cancer: Perfusion-Metabolic Correlation.

PURPOSE: The aim of this study was to investigate the relationship between whole-tumor CT perfusion and FDG PET/CT parameters in non-small cell lung cancer (NSCLC). METHODS: Twenty-five patients with NSCLC were prospectively included. CT perfusion parameters calculated were blood flow (BF), blood volume (BV), mean transit time, and peak enhancement intensity. SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated for PET/CT. Tumor diameter and volume were measured, and lesions were divided according to maximum axial diameter in more than 3 cm and 3 cm or less. The correlations between CT perfusion and PET/CT parameters were assessed in all tumors, as well as according to tumor diameter and volume. RESULTS: Lesion diameter and volume showed a negative correlation with BF and BV (r = -0.78, -0.78, -0.57, -0.48, respectively) and a positive correlation with mean transit time (r = 0.55, 0.65, respectively). The negative correlation between BF and lesion diameter and volume was confirmed in the subgroup of lesions of more than 3 cm (r = -0.68, -0.68, respectively). A positive correlation between SUVmax, SUVpeak, SUVmean, and lesion volume was observed (r = 0.50, 0.50, 0.46, respectively) and confirmed in lesions 3 cm or less (r = 0.81, 0.79, 0.78, respectively). Metabolic tumor volume and TLG showed a positive correlation with lesion diameter and volume in the overall population (r = 0.93, 0.87, 0.88, 0.90, respectively) and in lesions of more than 3 cm (r = 0.89, 0.84, 0.84, 0.79, respectively). Blood flow and BV showed a negative correlation with MTV and TLG (r = -0.77, -0.74, and -0.58, -0.48, respectively) in the overall population and with MTV in lesions of more than 3 cm (r = -0.69, -0.62, respectively). CONCLUSIONS: Perfusion and metabolic parameters seem to depend on tumor size. The bigger the tumor, the lower the BF and the BV and, conversely, the higher the SUVpeak, MTV, and TLG. This information would be useful in the clinical setting when diagnosing or treating NSCLC, especially with novel therapies and/or for radiation treatment modulation.

11C-Methionine-Avid Plasmablastic Lymphoma.

A 73-year-old woman had a diagnosis of a plasmablastic lymphoma by the excision of the right parotid gland. Two years after the diagnosis, the patient underwent a whole-body C-methionine PET/CT in order to evaluate the amino acid avidity of a scalp metastasis and for plasmablastic lymphoma restaging. C-methionine uptake was detected in the scalp, in several bone sites, and in the cricoid cartilage. Plasmablastic lymphoma is a subtype of B-cell lymphoma with an aggressive behavior and a poor prognosis. C-methionine appears to be a promising tracer for paraprotein-producing neoplasms.