18 F-FDG PET/CT imaging in pulmonary sarcomatoid carcinoma and correlation with clinical and genetic findings Abstract Objective Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer with poor prognosis. This study analyzed 18F-FDG PET/CT in PSC and possible correlations with the clinical and genetic findings. Methods Pre-operative 18F-FDG PET/CT findings and parameters of maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary lesion (MTV-P, TLG-P), and combination of primary lesion and metastases (MTV-C, TLG-C) were retrospectively analyzed in 24 patients with PSC confirmed by post-operative pathology. Tumor location, size, TNM stage, serum tumor markers, histopathological features, and mutations were also reviewed. Furthermore, progression-free survival (PFS) of 24 patients was analyzed. Results All 24 enrolled patients (20 men; 4 women; age: 62 ± 9 years) had single PSC, including 8 spindle cell carcinomas and 16 pleomorphic carcinomas. Serum levels of tumor markers were found to be abnormally increased sporadically. Six patients had central PSC, and 18 had peripheral PSC (diameter: 41 ± 16 mm). Eighteen lesions were located in the upper lobes of bilateral lungs, and 22 showed necrosis. Five cases were at TNM stage I, 12 at stage II, and 7 at stage III. The primary tumors were FDG avid in the 24 cases, with SUVmax of 17.2 ± 10.6. There were no correlations of SUVmax with tumor location, size, TNM stage, or histopathological subtypes. Programmed cell death ligand 1 (PD-L1) expression was detected in 21 cases (positivity rate: 87.5%). SUVmax of 17 lesions with PD-L1 expression degree ≥ 50% was obviously higher than that < 50% (P < 0.05). Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation was found in six cases, and their SUVmax was significantly higher than that without KRASmutation (P < 0.05). Furthermore, the median PFS of the 24 patients was 14 months, and 12-month and 24-month PFS rates were 55.9% and 27.8%, respectively. Only TLG-P and KRAS mutations of primary lesions were significantly associated with PFS. Conclusions PSC tended to present with intense 18F-FDG accumulation on PET/CT, and SUVmax was useful for assessing PD-L1 and KRAS expression of PSC. TLG-P and KRAS mutation were independent prognostic factors of PSC.

18F-FDG PET/CT in visceral leishmaniasis: uptake patterns in the context of a multiannual outbreak in Northern Italy Abstract Objectives Visceral leishmaniasis (VL) is the most severe manifestation of the infection caused by the protozoan Leishmania, recently on increase in Italy and Spain. The aim of the study was to describe FDG uptake patterns in VL patients (pts) who underwent 18F-FDG PET/CT. Methods A retrospective monocentric study of pts who underwent FDG PET/CT between 2008 and 2017 and later diagnosed with VL was performed. Semi-quantitative parameters were calculated in FDG-positive lesions: SUVmax, SUVmax spleen/SUVmax liver ratio (SLR), SUVmax focal/diffuse spleen ratio (FDR). Results Overall, 23 pts were included. PET/CT was negative in 2 immunocompromised pts, positive in 21/23 (91%) [6 spleen only, 2 spleen + nodes, 7 spleen + bone marrow (BM), 4 spleen + BM + nodes, 1 spleen + BM + lung, 1 BM only + nodes, 2 nodes only]. Splenic involvement was demonstrated in 20/23 (87%) pts. Two different splenic patterns were observed: diffuse (13/20 pts, mean spleen SUVmax = 7.3 ± 4.2 [4.0–14.1], mean SLR = 2.2 ± 1.6 [1.3–6.7]) and focal over diffuse (7/20 pts, mean SUVmax = 12.6 ± 4.5 [9.5–20.5], mean SLR = 2.8 ± 0.8 [2.1–4.4], mean FDR = 2.1 ± 0.8 [1.2–3.6]). Extra-splenic FDG-avid findings were detected in 15/21 pts (65%): bone marrow in 13/15 (mean SUVmax = 4.0 ± 1.3 [2.8–6.0]), nodes in 67/15 and lung in 1/15. Conclusions PET/CT demonstrated splenic FDG uptake in all immunocompetent VL pts; two splenic patterns (diffuse/focal over diffuse) were observed and indistinguishable from splenic involvement by other disorders. The most frequent extra-splenic FDG-positive sites were BM and lymph nodes. Considering the potential disease aggressiveness and recent outbreaks in north-eastern Italy, VL should be considered in the differential diagnosis of FDG-positive splenic findings in pts from endemic areas or reporting travels to endemic countries.

A reduced liver 18 F-FDG uptake may be related to hypoalbuminemia in patients with malnutrition Abstract Objective 18F-FDG PET/CT is a hybrid imaging method widely used as a useful, noninvasive imaging modality for evaluating various neoplastic diseases. When assessing the tumor uptake, the liver and the mediastinal blood pool are often used as a reference region. In daily clinical practice, the 18F-FDG uptake in the liver sometimes appears to decrease on PET images of patients with malnutrition. The purpose of this study was to investigate whether or not the liver 18F-FDG uptake is decreased in patients with malnutrition. Methods We retrospectively analyzed 246 patients who underwent 18F-FDG PET/CT from January 2018 to June 2018 and whose blood serum albumin was measured within 1 month of PET/CT. We compared the liver uptake and mediastinal blood uptake of patients with low serum albumin level (< 4.0 g/dl) and hypoalbuminemia (< 3.5 g/dl) with those with a normal serum albumin level (≥ 4.0 g/dl). Correlations between the liver and mediastinal blood uptake and the serum albumin level were also calculated. Results The maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) of the liver in 117 patients with low serum albumin were 3.1 ± 0.5 and 2.3 ± 0.3, respectively, while they were 2.9 ± 0.4, 2.0 ± 0.3 in 29 patients with hypoalbuminemia; these values were all significantly lower than the respective ones (3.4 ± 0.5, 2.5 ± 0.4) in 129 patients with normal serum albumin (all p < 0.001). The SUVmean of the mediastinal blood uptake in patients with hypoalbuminemia and normal serum albumin were 1.6 ± 0.2 and 1.7 ± 0.3, respectively (p = 0.053). The serum albumin level demonstrated a significantly positive, moderate correlation with the liver SUVmean, showing a regression line of y = 0.31x + 1.1 (r = 0.41, p < 0.001). Conclusion The liver 18F-FDG uptake tended to decrease in patients with hypoalbuminemia. In the patients with malnutrition, the mediastinal blood pool may be a more stable reference than the liver for evaluating the tumor activity because hypoalbuminemia is considered to less strongly influence the mediastinal blood pool than that in the liver.

Prediction of occult lymph node metastasis using SUV, volumetric parameters and intratumoral heterogeneity of the primary tumor in T1-2N0M0 lung cancer patients staged by PET/CT Abstract Objective The aim of this study was to identify whether PET/CT-related metabolic parameters of the primary tumor could predict occult lymph node metastasis (OLM) in patients with T1-2N0M0 NSCLC staged by 18F-FDG PET/CT. Methods 215 patients with clinical T1-2N0M0 (cT1-2N0M0) NSCLC who underwent both preoperative FDG PET/CT and surgical resection with the systematic lymph node dissection were included in the retrospective study. Heterogeneity factor (HF) was obtained by finding the derivative of the volume-threshold function from 40 to 80% of the maximum standardized uptake value (SUVmax). Univariate and multivariate stepwise logistic regression analyses were used to identify these PET parameters and clinicopathological variables associated with OLM. Results Statistically significant differences were detected in sex, tumor site, SUVmax, mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis and HF between patients with adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). OLM was detected in 36 (16.7%) of 215 patients (ADC, 27/152 = 17.8% vs. SQCC, 9/63 = 14.3%). In multivariate analysis, MTV (OR = 1.671, P = 0.044) in ADC and HF (OR = 8.799, P = 0.023) in SQCC were potent associated factors for the prediction of OLM. The optimal cutoff values of 5.12 cm3 for MTV in ADC, and 0.198 for HF in SQCC were determined using receiver operating characteristic curve analysis. Conclusions In conclusion, MTV was an independent predictor of OLM in cT1-2N0M0 ADC patients, while HF might be the most powerful predictor for OLM in SQCC. These findings would be helpful in selecting patients who might be considered as candidates for sublobar resection or new stereotactic ablative radiotherapy.

Limited role of carbidopa-assisted 18 F-FDOPA PET/CT in patients with sporadic non-functional gastroduodenal neuroendocrine neoplasms Abstract Objective To evaluate 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography/computed tomography (PET/CT) after carbidopa premedication to localize sporadic, well-differentiated, nonfunctioning gastroduodenal neuroendocrine neoplasms (NENs). Methods Ten patients undergoing staging carbidopa-assisted 18F-FDOPA PET/CT before endoscopic or surgical resection of gastroduodenal NENs were retrospectively selected. Preoperative imaging work up also included CT, magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) single-photon emission computed tomography/computed tomography (SPECT/CT) in ten, six, and eight patients, respectively. Histopathological diagnosis of primary NEN was the diagnostic standard of truth. Metastatic spread was defined as the presence of histologically proven nodal, visceral, and/or bone metastases. Results Tumors were located in the duodenal bulb in five patients, in descending duodenum in three, and in the gastric fundus in two. Three patients presented with both lymph nodes and distant metastases, and two with exclusive lymphatic spread. CT and MRI detected primary tumor in one out of ten and three out of six patients, respectively. SRS failed to detect intestinal NEN in all cases. 18F-FDOPA PET/CT detected four primary NENs (one gastric and three duodenal tumors) and was false negative in six patients. NENs missed by 18F-FDOPA PET/CT were smaller than 10 mm in two cases and measured about 30 mm in three patients. The remaining tumor was detected only on blind endoscopic biopsy. Among patients who underwent both 18F-FDOPA PET/CT and SRS, three presented discordant results for primary tumor detection (PET/CT positive/SRS negative) and five showed concordant negative studies. 18F-FDOPA PET/CT correctly identified all three patients with both nodal and visceral metastatic disease and failed to detect lymph node metastases in both N+ M0 patients. Conclusions 18F-FDOPA PET/CT is not sufficiently accurate for localization of primary well-differentiated nonfunctioning sporadic gastroduodenal NENs. 18F-FDOPA PET/CT’s value for the assessment of visceral and lymph node metastases needs to be clarified in multicenter trials including a larger number of patients.

Combining the radiomic features and traditional parameters of 18 F-FDG PET with clinical profiles to improve prognostic stratification in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery Abstract Objectives To investigate the role of the traditional and radiomic parameters of 18F-FDG PET for predicting the outcomes of patients with esophageal squamous cell carcinoma (SqCC). Methods Forty-four patients with primary esophageal SqCC who underwent neoadjuvant chemoradiotherapy (CCRT) followed by esophagectomy (tri-modality treatment) were retrospectively analyzed. All patients underwent 18F-FDG PET/CT before and after neoadjuvant CCRT. The radiomic features were calculated using the pre-treatment PET scan. Pre-treatment radiomic features and changes in the PET-derived traditional parameters after neoadjuvant CCRT were analyzed according to the pathological response to esophagectomy, disease-free survival (DFS), and overall survival (OS). We further developed a scoring system based on the independent survival prognosticators and compared our model to the traditional TNM staging system and surgical pathology. Results A pre-treatment primary tumor histogram entropy ≥ 3.69 predicts an unfavorable response to neoadjuvant CCRT (OR = 19.25, p = 0.009). An SUVmax reduction ratio ≤ 0.76, a pre-treatment primary tumor code similarity ≤ 0.0235, and incomplete pathological remission were independently associated with poor OS (p = 0.019, 0.033, and 0.038, respectively) and DFS (p = 0.049, 0.021, and 0.009, respectively). The three survival prognosticators were used to construct a scoring system (score 0–1, 2, and 3). Patients with a score of 2 or 3 had a significantly worse survival outcome than those with a score of 0–1 (HRs for OS: 3.58 for score 2, and 15.19 for score 3, p < 0.001; HRs for DFS: 1.39 for score 2 and 6.04 for score 3, p = 0.001).This survival prediction model was superior to the traditional TNM staging system (p < 0.001 versus p = 0.061 for OS, and p = 0.001 versus p = 0.027 for DFS) and the model based on surgical pathology (p < 0.001 versus p = 0.049 for OS, and p = 0.001 versus p = 0.022 for DFS). Conclusions The 18F-FDG PET-derived radiomic parameter is useful for predicting the surgical pathological response in patients with esophageal SqCC treated with the tri-modality method. Using a combination of traditional and radiomic PET parameters with clinical profiles enables better stratification of patients into subgroups with various survival rates.

The use of molecular volumetric parameters for the evaluation of Lu-177 PSMA I&T therapy response and survival Abstract Purpose The primary aim of this study was to evaluate the volumetric therapy response via Ga-68 PSMA I&T PET/CT in patients treated with Lu-177 PSMA I&T therapy. The secondary purpose was to determine the impact of volumetric parameter responses to overall survival. Methods PSMA tumor volumes (PSMA-TV) and tumor lesion PSMA expressions (TL-PSMA) were calculated with a semi-automatic program on Ga-68 PSMA I&T PET/CT images that were obtained before and after Lu-177 PSMA I&T therapies with 19 patients. The median overall survival was compared with PSMA-TV, TL-PSMA, SUVmax, PSA, and alteration in PERCIST criteria. Results PSMA-TV values were decreased in 12 patients (63%), and TL-PSMA values were decreased in 15 patients (79%) following the therapy. The SUVmax and the PSA values were also decreased in 14 (74%) and 10 (53%) patients, respectively. The complete remission (CR) was observed in two patients (10%). The partial response (PR) and progressive disease were observed in 6 (32%) and 11 (58%) patients, respectively, according to PRECIST criteria. The survival rates were statistically significant in patients with a decrease in PSMA-TV and TL-PSMA values than patients without any decrease (p 0.001, p < 0.001, respectively). However, the survival rates did not differ in responders (PR or CR) and non-responders according to the PERCIST criteria (p 0.232). The survival rates did not also differ in responders and non-responders according to the SUVmax and PSA values (p 0.140, p 0.206, respectively). Conclusions Molecular and volumetric parameters are beneficial in the assessment of Lu-177 PSMA I&T therapy response. Although the number of patients is small, TL-PSMA response, which includes both the tumor volume and PSMA expression in tumor, may be considered as the most valuable parameter for the evaluation of the therapy response and the prediction of survival rate.

Development of visual scoring system with Tc-99m DMSA renal scintigraphy to predict the risk of recurrence of symptomatic urinary tract infections in pediatric patients Abstract Objective Vesicoureteral reflux (VUR) is a major risk factor for recurrent symptomatic urinary tract infection (UTI) in pediatric patients. In addition, dimercaptosuccinic acid renal scintigraphy (DMSA) is an important diagnostic modality of VUR. However, the value of DMSA for predicting recurrent pediatric UTI has not been studied. Therefore, we aimed to develop visual scoring system (VSS) with DMSA to predict the risk of recurrence of symptomatic urinary tract infection in pediatric patient under the age of 24 months. Methods Pediatric UTI patients who visited our tertiary hospital emergency department and underwent DMSA for initial work-up from January 2006 to December 2014 were reviewed retrospectively. We developed a VSS with Tc-99m DMSA renal scintigraphy. We compared sensitivity and specificity between VSS with DMSA and other variables in predicting recurrent symptomatic UTI. Laboratory indices for systemic inflammation, abnormal finding on ultrasonography, VUR on voiding cystourethrogram (VCUG), and the VSS with DMSA were considered as variables. In addition, we used Kaplan–Meier estimator analyses and Cox proportional regression analyses to evaluate the predictive value of each variable for the recurrence of symptomatic UTI. Results A total of 338 patients were enrolled. During the follow-up period, 42 patients (12.4%) had UTI recurrence. Visual scoring with DMSA resulted in 69.1% sensitivity and 79.4% specificity with an optimal cut-off value of score 2 (AUC = 0.790, p < 0.001). Significant predictive factors associated with recurrent symptomatic UTI were CRP ≥ 67.0 mg/L, VUR on VCUG and VSS with DMSA ≥ score 2. On multivariate analysis, the visual score with DMSA was the only independent prognostic factor for recurrent symptomatic UTI (p < 0.001; adjusted hazard ratio = 7.522; 95% CI = 2.799–20.224). Conclusion High scores in VSS with DMSA were associated with frequent recurrence and short recurrence periods in pediatric UTI patients. VSS with DMSA can stratify risk of recurrence in pediatric UTI patients.

Searching for diagnostic properties of novel fluorine-18-labeled d -allose Abstract Objective Two fluorine-18-labeled analogues, 3-deoxy-3-[18F]fluoro-d-allose (3-[18F]FDA) and 6-deoxy-6-[18F]fluoro-d-allose (6-[18F]FDA), were synthesized and their potentials of diagnostic property were characterized. Methods In vitro rat red blood cell (RBC) transport and phosphorylation by yeast hexokinase were evaluated in comparison with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). The rate of protein binding in pooled human serum was measured by an ultrafiltration method. In vivo metabolite analysis in mice was also performed. Biodistribution, urine excretion, and in vivo renal kinetics in mice were compared with 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS). Results Rat RBC uptake of 3- and 6-[18F]FDA (7.8 ± 2.5%ID and 10.2 ± 4.8%ID, respectively) was significantly lower than that of [18F]FDG (44.7 ± 8.7%ID). RBC uptake of 3-[18F]FDA was inhibited by d-glucose (30%) and cytochalasin B (40%), indicating the involvement of GLUT1-dependent transport. In contrast, 6-[18F]FDA transport was not inhibited by d-glucose and cytochalasin B. 3- and 6-[18F]FDA were not phosphorylated by yeast hexokinase under the conditions that result in 60% conversion of [18F]FDG into [18F]FDG-6-phosphate within 30 min. Serum protein binding of 3- and 6-[18F]FDA was negligible. Metabolic transformation of both tracers was not detected in plasma and urine at 30 min after injection. The highest tissue uptake of both tracers was observed in kidneys. Heart and brain uptake of both tracers was below blood levels throughout the biodistribution studies (until 120 min after injection). No significant uptake in the bone was observed, indicating the absence of de-fluorination in mice. In vivo PET imaging visualized rapid excretion of the administered 3- and 6-[18F]FDA from the kidneys, with minimal tracer accumulation in other organs. The urine excretion rate of 3-[18F]FDA was much lower than that of 6-[18F]FDA and [18F]FDS. Conclusions 3- and 6-[18F]FDA might be unsatisfactory for tumor imaging. In contrast, these tracers demonstrated high levels of kidney uptake and excretion, low serum protein binding, and high metabolic stability as preferable properties for renal imaging. Notably, the urine excretion rate and kidney uptake kinetics of 6-[18F]FDA were comparable with those of the potential renal imaging agent [18F]FDS. Further validation studies in animal models are required to confirm the feasibility of 6-[18F]FDA as a functional renal imaging agent.

Impact of decompressive craniectomy on brain perfusion scintigraphy as an ancillary test for brain death diagnosis Abstract Objectives Decompressive craniectomy is occasionally performed for patients with impending brain death, which is intended to relieve critically elevated intracranial pressure to keep effective intracranial perfusion. It has been in debate if this surgery later affects the result of brain perfusion scintigraphy performed as an ancillary test in the course of brain death diagnosis because rigid closed skull is deemed essential to elevate intracranial pressure to the point of total absence of intracranial radiotracer uptake on scintigraphy. The purpose of this study is to elucidate the impact of decompressive craniectomy on the result of brain perfusion scintigraphy in patients with suspected brain death. Methods This retrospective cross-sectional study included consecutive 151 brain perfusion scintigraphy performed in 138 patients with suspected brain death from various causes (male 82 patients, female 56 patients; range 0–74 years; mean age 36.6 years). All exams were indicated due to inconclusive clinical diagnosis of brain death. The scintigraphy protocol consists of immediate flow phase and delayed parenchymal phase planar imaging. Additional SPECT imaging was performed in 15 studies in 14 patients. The results, positive or negative brain flow, were compared between patients with and without decompressive craniectomy using Chi-squared test. As there were patients with repeat studies, analysis was performed for both initial and final exam results. Same dataset was used for initial and final exams in patients with only one exam. Results Out of 138 patients, 15 patients underwent decompressive craniectomy (11%) and 123 patients were managed medically (89%). On the initial exam, negative brain flow was demonstrated in 11 of 15 patients with craniectomy (73.3%) and 106 of 123 patients without craniectomy (86.2%). On the final exam, negative brain flow was demonstrated 12 of 15 patients with craniectomy (80%) and 111 of 123 patients without craniectomy (90.2%). There were no statistically significant differences between the two groups on both initial and final exams (p = 0.19 and 0.23, respectively). Conclusion In patients with suspected brain death, history of decompressive craniectomy does not affect the result of brain perfusion scintigraphy.