The relationship between 18F-FCH uptake intensity and cell content in parathyroid lesions.

PURPOSE: To investigate the relationship between cell content and histopathological features of parathyroid lesions and 18F-FCH uptake intensity on PET/CT images. METHODS: Patients with primary hyperparathyroidism (age > 18) who were referred to 18F-FCH PET/CT were involved. All patients underwent parathyroidectomy. Correlation of SUVmax with following factors were statistically analysed: serum PTH, Ca, P levels and histopathological parameters, total absolute amounts of chief cell, oxyphyllic cell and clear cell components calculated by the multiplication of the volume of the parathyroid lesion and the percentage of each type of cell content (called as Absolutechief, Absoluteoxyphyllic and Absoluteclear reflecting the total amount of each cell group). RESULTS: A total of 34 samples from 34 patients (6M, 28F, mean age: 53.32 ± 15.15, min: 14, max: 84) who had a positive 18F-FCH PET/CT localizing at least one parathyroid lesion were involved. In the whole study group, SUVmax was found to be correlated with the greatest diameter and volume of the lesion and Absolutechief (p = 0.004, p = 0.002 and p = 0.035, respectively). In the subgroup analysis of 28 samples with longest diameter > 1 cm, the correlation between SUVmax and Absolutechief remained significant (p = 0.036) and correlation between SUVmax and volume and longest diameter became stronger (p = 0.011 and p > 0.001, respectively). No correlation was found between SUVmax and Absoluteoxyphyllic or Absoluteclear. CONCLUSIONS: There might be a relationship between 18F-FCH uptake intensity and chief cell content in patients with parathyroid adenoma. Further studies with larger patient groups would be beneficial to support the data.

Myocardial perfusion SPECT findings in postCOVID period.

PURPOSE: To investigate if (i) the risk of ischemia on myocardial perfusion scan (MPS), (ii) number of coronary angiographies (CAG) performed, and (iii) necessity for invasive (stent implantation or coronary artery bypass grafting (CABG)) or medical treatment increased in patients infected with COVID-19. METHODS: Patients who were referred to MPS between August 2020 and April 2021 with a history of active symptomatic COVID-19 infection (confirmed by PCR positivity) in the last 6 months were involved in the study group. Age-and gender-matched control group was composed of randomly chosen patients who attended for MPS between January 2019 and September 2019, before pandemic. Frequency of ischemia, CAG, and invasive or medical treatments were compared between groups. RESULTS: Ischemia was reported more frequently in the study group (p < 0.001). In clinical evaluation, regardless of the MPS results, the necessity for invasive evaluation with CAG and treatment (either medical therapy or invasive interventions) was higher in the study group (p = 0.006 and p = 0.015). It was also true for patients with abnormal MPS results (p = 0.008 and p = 0.024) but not for the patients with ischemia (p = 0.29 and p = 0.06). CONCLUSION: There exists a significant increase in the frequency of ischemia on MPS, undergoing CAG, stent implantation or CABG, and initiation of medical therapy in patients with a history of COVID-19 infection in the last 6 months. MPS is a reliable method in patients who present with cardiovascular symptoms in the late COVID period.

Prognostic value of metabolic parameters on baseline 18F-FDG PET/CT in small cell lung cancer.

BACKGROUND: Maximum standardized uptake value (SUVmax) is the primary quantitave parameter given in 18F-FDG PET/CT reports. Calculations derived from three dimensional metabolic volumetric images have been proposed to be more successful than SUVmax alone in prognostification with a lower interobserver variability in many cancers. We aimed to determine the prognostic value of metabolic parameters derived from 18F-FDG PET/CT studies in small cell lung cancer (SCLC) patient population with a long follow-up time. METHODS: In this study, 38 consecutive SCLC patients (34M, 4F, age:65.76 ±8.18 years) who were referred to 18F-FDG PET/CT for staging between October 2006-January 2011 were included. SUVmax, SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. Overall survival (OS) was calculated from the date of the initial PET/CT to death from any cause. Survival tables were obtained and Kaplan Meier curves were reconstructed. Mantel-Cox regression analysis was performed in order to investigate if any of these parameters have an effect on survival along with other clinical risk factors. RESULTS: Median SUVmax, SUVmean, SUVpeak, MTV, TLG and LDH values were calculated as 13.9 g/dL, 6.4 g/dL,10.69 g/dL, 147 cm3, 1898.52 and 375U/L respectively. Median follow-up was 761.23±873.21 days (25.37 months, range:110-3338 days). Since basal 18F-FDG PET/CT scans, all patients were lost in the follow-up except for two patients. MTV was a significant prognostic factor in SCLC patients. Estimated mean survival times were 261.0±45.6 (95% CI: 171.6-350.3) days in patients with MTV value above the calculated median 147, and 577.0±124.0 (95% CI: 333.7-820.2) days in patients with MTV<147. The difference was statistically significant with a P=0.037. CONCLUSIONS: Baseline whole body MTV reflecting total tumor load is a prognostic index in SCLC. SUV is insufficient to predict prognosis.

Detectability of 18F-choline PET/MR in primary hyperparathyroidism.

PURPOSE: We aimed to evaluate the power of 18F-fluorocholine (FCH) positron emission tomography/magnetic resonance (PET/MR) imaging in unlocalized primary hyperparathyroidism. METHODS: Thirty-four patients were included. In 17/34 patients, PET/MR was performed immediately after a negative 18F-FCH PET/CT. Sensitivity, specificity, positive and negative predictive values were calculated for MR only (blinded to PET data) and PET only (blinded to MR data) findings. RESULTS: 18F-FCH PET/MR was positive in 26/34 (76%) patients. PET/MR was also positive in 12/17 (71%) patients with a negative PET/CT. Among 11/34 (32%) patients where 18F-FCH PET-only and MR-only results were discordant, MR was false positive in 7/11 patients (3/7 of the lesions were not 18F-FCH avid and in 4/7 of them PET and MRI pointed different locations. Postoperative histopathology revealed that 18F-FCH-positive ones were true positives). Sensitivity, specificity, PPV, NPV and accuracy of neck MR evaluated blinded to PET data were 80%, 50%, 70%, 64% and 68%, respectively, and all were calculated as 100% for PET/MR. CONCLUSION: 18F-FCH PET/MR is very effective in preoperative localization of parathyroid adenomas even if 18F-FCH PET/CT is negative. Neck MR alone is insufficient in detecting parathyroid adenomas but PET/MR combination helps in precise localisation.

Radiomics analysis of uterine tumors in 18F-fluorodeoxyglucose positron emission tomography for prediction of lymph node metastases in endometrial carcinoma.

BACKGROUND: In this single-center study, we aimed to analyze texture features of primary uterine lesions on 18F-FDG PET/CT to predict lymph node metastases. METHODS: Totally, 157 (mean age: 62 ± 10.2 years) patients were included in the analysis. Histopathological examination results were considered as the standard reference for nodal involvement. On 18F-FDG PET/CT images, only the primary tumor was segmented. SUVmax, SUVmean, SUVpeak, MTV, and TLG of primary uterine lesions were calculated for analyses. For texture analysis first, second, and higher-order texture features were calculated. RESULTS: Mean diameter of primary uterine lesions was calculated as 35± 18.1 mm. Lymph node metastases were detected in 19% of patients in histopathological examination of surgical materials. While 26 patients had pelvic lymph node metastases, 19 patients had additional paraaortic lymph node metastases. On radiomics analysis for 20 features, a significant difference was found between patients with and without lymph node metastasis. With using data mining methods GLZLM ZLNU, EntropyGLCM, Entropyhisto, GLRLM LRHGE, GLZLM HGZE, GLZLM SZHGE, GLRLM HGRE, GLRLM SRHGE were found significant radiomics features to predict lymph node metastasis with a diagnostic accuracy of 0.8. DISCUSSION: The radiomics analysis of intratumoral heterogeneity is a promising method for improving triage of the patients for lymph node dissection in endometrial carcinoma.

Prognostic importance of prostatic specific antigen response in patients who received Lutetium-177 prostate-specific membrane antigen treatment for castration resistant prostate cancer.

BACKGROUND: This study aims to analyze the prognostic importance of serum prostate specific antigen (PSA) response in patients who received radioligand therapy (RLT) with Lu-177 Prostate-specific membrane antigen (PSMA) for their castration-resistant prostate cancer. METHODS: Thirty consecutive patients who received Lu-177 PSMA treatment for their castration-resistant prostate carcinoma were included. All the patients had undergone Ga-68 PSMA PET/CT scanning before Lu-177 PSMA therapy, which revealed multiple metastases. Patients were treated with a fixed dose (180 mCi) of Lu-177 PSMA at six to eight weeks intervals. PSA response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Serum PSA response was classified as PSA progression (25% increase over the baseline and an increase in the absolute-value PSA level by at least 5 ng per millilitre), any <50% decline or ≥50% decline. PSA response was evaluated six weeks after every cycle. Response evaluation with radiological imaging and Ga-68 PSMA PET/CT were performed before the first cycle and eight weeks after the last cycle. RESULTS: Thirty patients were treated with a total of 171 cycles (median 4, range 3-7) of Lu-177 PSMA. A decline in serum PSA of ≥50% was detected in ten patients (33%) while a decline in PSA of any amount was observed in fifteen (50%) patients after the first cycle. After the last cycle, a decline in PSA ≥50% and of any amount was seen in thirteen (43%) and fourteen (46%) patients, respectively. Of the fifteen patients who were not responder after the first cycle, three (20%) had a decline in PSA of any amount after the completion of the RLT. Moreover, of the 20 patients who did not have a ≥50% decline in PSA level after the first cycle, four (20%) became responder after the last cycle. Regarding serum PSA response after the first cycle, median OS was significantly higher for patients who had ≥50% decline in PSA level with 21.0±10.0 (95% CI: 1.2-40.7) months compared to patients who had not with 8.0±2.6 (95% CI: 2.7-13.2) months (P=0.012). A decline in PSA of any amount after the first cycle did not have a significant impact on median OS (12.0±1.1 vs. 6.0±2.5 months, P=0.08). The decline in serum PSA level after the last cycle of treatment had a significant impact on OS. Median OS for the decline in PSA of any amount was calculated as 13.0±1.0 (95% CI: 10.9-15.0) months for responders and 6.0±1.9 (95% CI: 2.2-9.7) months for non-responders (P=0.016). Considering ≥50% of decline as a response, median OS was 21.0±5.8 (95% CI: 9.5-32.4) months for responders and 6.0±3.0 (95% CI: 0.1-11.8) months for non-responders (P=0.026). CONCLUSIONS: Serum PSA level during RLT with Lu-177 PSMA remains a clinically significant factor to predict OS times. About twenty percent of patients who were not responder after the first cycle could become responder after the last cycle. However, patients without PSA response after completion of all cycles should be closely followed-up. Non-responder patients can achieve a response with further treatments.

Photocatalytically Active Graphitic Carbon Nitride as an Effective and Safe 2D Material for In Vitro and In Vivo Photodynamic Therapy.

Thanks to its photocatalytic property, graphitic carbon nitride (g-C3 N4 ) is a promising candidate in various applications including nanomedicine. However, studies focusing on the suitability of g-C3 N4 for cancer therapy are very limited and possible underlying molecular mechanisms are unknown. Here, it is demonstrated that photoexcitation of g-C3 N4 can be used effectively in photodynamic therapy, without using any other carrier or additional photosensitizer. Upon light exposure, g-C3 N4 treatment kills cancer cells, without the need of any other nanosystem or chemotherapeutic drug. The material is efficiently taken up by tumor cells in vitro. The transcriptome and proteome of g-C3 N4 and light treated cells show activation in pathways related to both oxidative stress, cell death, and apoptosis which strongly suggests that only when combined with light exposure, g-C3 N4 is able to kill cancer cells. Systemic administration of the mesoporous form results in elimination from urinary bladder without any systemic toxicity. Administration of the material significantly decreases tumor volume when combined with local light treatment. This study paves the way for the future use of not only g-C3 N4 but also other 2D nanomaterials in cancer therapy.

Predictor of 68Ga PSMA PET/CT positivity in patients with prostate cancer.

BACKGROUND: The aim of this study was to evaluate predictive factors of 68Gallium (68Ga) prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) positivity. METHODS: Relationships between serum prostate specific antigen (PSA), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels, Gleason Score (GS) and positivity of 68Ga PSMA PET in patients who underwent 68Ga PSMA PET/CT for restaging for PCa were evaluated retrospectively. RESULTS: One hundred and four (median age: 67; range: 51-88) patients were included in this study. Of these patients, PSMA PET was positive in 75 (72%) patients. Mean serum PSA levels for PET negative and positive groups were 0.76±1.00 and 180.85±324.93 ng/mL (P<0.001). The sensitivity and specificity of 68Ga PSMA PET/CT for detection of disease recurrence were calculated as 92% and 80%, respectively, for the 1.4 ng/mL PSA cut-off and 92% and 90%, respectively, for the 2 ng/mL PSA cut-off values. The positivity rates for patients with PSA levels <1.4 ng/mL and ≥1.4 ng/mL were 21% and 90%, respectively (P<0.001). CONCLUSIONS: 68Ga PSMA PET/CT seems to be a highly sensitive in patients with early PSA recurrence. Patients with higher GS and early PSA recurrence could benefit from 68Ga PSMA PET/CT.

Optimizing PSMA Radioligand Therapy for Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Meta-Analysis.

The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of 177Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT.

Functional compared to anatomical imaging in the initial evaluation of patients with suspected coronary artery disease: An international, multi-center, randomized controlled trial (IAEA-SPECT/CTA study).

OBJECTIVE: To test the hypothesis that, in the initial evaluation of patients with suspected coronary artery disease (CAD), stress myocardial perfusion imaging (MPI) would result in less downstream testing than coronary computed tomographic angiography (CCTA). METHODS: In this international, randomized trial, mildly symptomatic patients with an intermediate likelihood of having CAD, and asymptomatic patients at intermediate risk of cardiac events, underwent either initial stress-rest MPI or CCTA. The primary outcome was downstream noninvasive or invasive testing at 6 months. Secondary outcomes included cumulative effective radiation dose (ERD) and costs at 12 months. RESULTS: We recruited 303 patients (151 MPI and 152 CTA) from 6 centers in 6 countries. The initial MPI was abnormal in 29% (41/143) and CCTA in 56% (79/141) of patients. Fewer patients undergoing initial stress-rest MPI had further downstream testing at 6 months (adjusted OR 0.51, 95% CI 0.28-0.91, P = 0.023). There was a small increase in the median cumulative ERD with MPI (9.6 vs. 8.8 mSv, P = 0.04), but no difference in costs between the two strategies at 12 months. CONCLUSION: In the management of patients with suspected CAD, a strategy of initial stress MPI is substantially less likely to require further downstream testing than initial testing with CCTA. TRIAL REGISTRATION: clinicaltrials.gov identification number NCT01368770.

Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/CT in Prediction of Uterine Risk Factors and Lymph Node Metastasis: An Analysis of 111 Endometrioid Endometrial Cancer Patients.

INTRODUCTION: This study evaluated the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) in the detection of lymph node metastases and the association between uterine maximum standardized uptake values (SUVmax) and the histopathological features in endometrial cancer patients. MATERIALS AND METHODS: Patients with endometrioid endometrial cancer underwent preoperative 18F-FDG PET/CT imaging and were staged surgically. 18F-FDG PET/CT findings were compared with final pathology reports. Grade 3 histology or grade 2 histology with myometrial invasion ≥50% was established as a high risk feature. RESULTS: One hundred and eleven patients were analysed. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT in the detection of lymph node metastasis in all patients (n = 111) were 67, 96, 93, 60 and 97%, respectively. In the high-risk group, sensitivity, specificity, accuracy, PPV and NPV of 18F-FDG PET/CT were 75, 92, 91, 60 and 96%, respectively. Uterine SUVmax was found to be associated with myometrial invasion, grade and cervical stromal involvement. CONCLUSIONS: 18F-FDG PET/CT has limited sensitivity and accuracy in detecting lymph node metastasis. Therefore, as of now, it is not accepted as a modality that can replace lymphadenectomy. SUVmax values can predict high-risk factors.

Assessment of Gastric Emptying in Patients with Autoimmune Gastritis.

BACKGROUND AND AIM: Symptoms of patients with autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any delay in gastric emptying of solid food exists in patients with autoimmune gastritis and, if so, to identify the factors that might affect delayed gastric emptying. METHODS: A total of 165 patients (106 women) diagnosed as having autoimmune gastritis were analyzed by means of a gastric emptying test. All patients underwent a standardized scintigraphic gastric emptying study. Patients with delayed gastric emptying and normal gastric emptying tests were then compared by means of factors that might affect gastric emptying. Also 65 patients with functional dyspepsia who had a gastric emptying study constituted the control group. RESULTS: The median gastric emptying T ½ time was 127.43 min (min-max 50-953) for patients with AIG and 81 min (min-max 21-121.6) for functional dyspepsia patients (p < 0.001), and median percent retention at 2 h was 63.8 versus 20.2 (p < 0.001). In multivariate analysis, parameters that affected gastric emptying T ½ time were found as serum gastrin level (OR 1.002, 95 % CI 1.001-1.004, p < 0.001, chronic inflammation (OR 3.689, 95 % CI 1.44-9.39, p < 0.001), and increase in the degree of the atrophy of the gastric mucosa (OR 8.96, 95 % CI 2.98-26.93, p < 0.001). CONCLUSIONS: In patients with autoimmune gastritis, gastric emptying is generally delayed. Autoimmune gastritis is an important etiology to explain the finding of delayed gastric emptying on a radionuclide test. This new finding is likely to be relevant to clinicians when evaluating and initiating appropriate medical treatment for patients with autoimmune gastritis manifesting upper gastrointestinal symptoms.

Relationships between autonomic nerve function and gastric emptying in patients with autoimmune gastritis.

PURPOSE: Autonomic nervous system dysfunction exists in autoimmune diseases. Symptoms of autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any autonomic dysfunction exists in autoimmune gastritis patients, and if so, to clarify the relationship between the autonomic nervous dysfunction, delayed gastric emptying, and gastrointestinal symptoms. METHODS: 75 patients (50 women, mean age 56.73 ± 11.77) diagnosed with autoimmune gastritis were investigated by means of autonomic nervous system and gastric emptying tests. All patients underwent a standardized scintigraphic gastric emptying study and five tests evaluating autonomic nervous system. Patients with autonomic nervous system dysfunction were then analyzed and compared by means of existence of delayed gastric emptying and gastrointestinal symptoms. RESULTS: 62 patients had autonomic nervous system dysfunction (14 mild, 40 moderate, and 8 severe autonomic dysfunction). The mean total score of autonomic tests was 3.85 ± 2.35. Total autonomic score of patients (n = 60) with delayed gastric emptying was significantly higher than patients (n = 15) with normal gastric emptying (4.68 ± 1.7 vs. 1.53 ± 0.58, p < 0.001). Mean gastroparesis cardinal symptom index was significantly higher in patients (n = 60) with delayed gastric emptying half-time compared to patients (n = 15) with normal gastric emptying half-time (1.89 ± 1.16 vs 0.4 ± 0.3, p < 0.001). CONCLUSIONS: Most of patients with autoimmune gastritis also have autonomic nerve dysfunction. There is a close relationship between autonomic nervous system dysfunction and delayed gastric emptying. Gastroparesis cardinal symptom index has a high sensitivity and specificity in predicting both autonomic nerve function and delay in gastric emptying.

The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the primary staging of rectal cancer.

BACKGROUND: In this study we aimed to determine the need for 18F-flourodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the preoperative staging of rectal carcinoma in our large patient group according to level and location of tumor. METHOD: Totally, 97 patients diagnosed with primary rectal adenocarcinoma between May 2009 and July 2011 were included in the study. Preoperative staging was performed by evaluating contrast-enhanced thoracic, abdominal, and pelvic computed tomographies. After staging by conventional methods, all patients underwent an 18F-FDG PET/CT. In all cases, the relationship between 18F-FDG uptake and gender, tumor height at the anal canal, localization in the rectal wall, plasma carcinoembryonic antigen levels, histopathological tumor type, and tumor stage were examined. RESULTS: While the ceCT was normal in 4 (4%) patients, it was positive for the rectum in 93 (95%), pelvic lymph nodes in 22 (22%), and distant metastases in 14 (14%) (liver (8), lung (8), bone (2), distant lymph nodes (6), and uterus (1)). Using computed tomography, disease stages were determined as stage 0, 1, 2, 3, and 4 in 4, 8, 48, 23, and 14 patients, respectively; 18F-FDG PET/CT was normal in two (2%) patients. The mean SUVmax of FDG-positive rectal tumors was calculated as 17.31 ± 9.37. Additionally, 18F-FDG uptake was seen in pelvic lymph nodes in 15 (15%) patients and in distant organs in 24 (24%) patients (liver (9), lung (12), bone (5), distant lymph nodes (11), uterus (1), and sigmoid colon (1)). According to an 18F-FDG PET/CT, 2, 7, 47, 20, and 21 patients were staged as stage 0, 1, 2, 3, and 4, respectively. In 14 patients (14.4%), the stage of the disease was either changed, and there was a need to make adjustments to the patient's treatment strategy (n = 10), or the type of operation was changed (n = 4). In seven patients (0.7%), findings from 18F-FDG PET/CT images did not require any changes of the treatment plan. CONCLUSION: F-FDG PET/CT provides new findings in addition to conventional techniques in the staging of primary rectal cancer. These findings could change the patients' treatment strategies.

Imaging of Hypoxia in Liver Tumors With 18F-FMISO PET Before Selective Internal Radiotherapy With 90Y Microspheres.

ABSTRACT: Hypoxia is a known cause of resistance to radiotherapy and chemotherapy. Although there are multiple studies in external radiation therapies based on hypoxia PET, the effect of hypoxia in radioembolization is largely unknown. Here we present 2 cases of hepatocellular carcinoma patients from a prospective study with different lesion characteristics on pretreatment 18F-FMISO PET and varying responses on 18F-FDG PET.

Comparison of 68Ga-PSMA PET/CT and 18F-PSMA PET/CT of a Patient with Prostate Cancer Recurrence on Urinary Bladder Wall.

Prostate cancer is one of the most prevalent cancers in the world. After radical prostatectomy, prostate-specific antigen (PSA) levels are usually used as a marker of recurrence for prostate cancer. In the case of increased PSA levels, 68Ga-prostate-specific membrane antigen (PSMA) or 18F-PSMA, a new alternative, can be performed for the detection of recurrent disease. We report a case of a 49-year-old male patient with increasing PSA levels who was previously operated 8 years ago. Although no obvious pathological uptake was detected in 68Ga-PSMA positron emission tomography/computed tomography (PET/CT), 18F-PSMA PET/CT revealed a lesion with pathological uptake on the urinary bladder wall.