Multicenter quantitative 18F-fluorodeoxyglucose positron emission tomography performance harmonization: use of hottest voxels towards more robust quantification.

Background: Harmonization methods reduce variability between different make and models of positron emission tomography (PET) scanners. The study aims to explore harmonization strategies that lead to comparable and robust quantitative metrics in a multicenter setting. Methods: NEMA IEC Phantom data acquisition was performed for low and high spheres-to-background ratios (SBR4:1 and 10:1) on six PET/CT (computed tomography) scanners. Different reconstruction sets, including the number of sub-iterations, number of subsets, and full width at half maximum (FWHM) for each scanner, were evaluated towards optimized and harmonized reconstruction settings. Recovery coefficients (RCs) of four quantitative metrics, including standardized uptake value (SUV)max, SUVISO-50 (SUVmean in 50% isocontour), SUVpeak, and mean uptake of 10 highest concentration voxels were evaluated as RCmax, RCISO-50, RCpeak, and RC10V, representing percent difference relative to the static ground truth case as functions of sphere sizes. A set of image reconstruction parameters was proposed for harmonized reconstruction to minimize variability between scanners. The root mean square error (RMSE), curvature, and reproducibility were examined. The proposed reconstruction protocols for harmonization and standard clinical reconstruction settings were compared to each other across all scanners. Results: A significant difference (P value <0.0001) was observed in the aforementioned quantitative metrics between SBR10 and SBR4. Reconstruction parameter sets with the smallest RMSE and RC values within 10% bias were identified as the best candidate for harmonization. The coefficient of variation of the mean value of RCs (CVMRC) shows a remarkable reduction of about 28%, 26%, 32%, and 19% in harmonized reconstruction settings for MRCmax, MRCISO-50, MRCpeak, and MRC10V, respectively. CVMRC for MRC10V in the harmonized reconstruction setting was 5.9% in SBR4, while the smallest value in SBR10 belongs to MRCpeak, with a value of 5.8%. The reproducibility of RC is improved by deriving the value from ten hottest voxels and is equally reproducible with RCpeak. Compared to RCmax and RCISO-50, the variability is reduced by 18% and 22% if ten voxels are pooled. Conclusions: Harmonizing PET/CT systems with and without point spread function/time of flight (PSF/TOF) using various vendor-developed image reconstruction algorithms improves the quantification reproducibility. RC10V, likewise RCpeak, is superior to the rest of the quantitative indices in terms of accuracy and reproducibility and helpful in quantifying lesion volume below 1 mL.

The effect of trehalose administration on vascular inflammation in patients with coronary artery disease.

BACKGROUND: In recent years, several trials investigated the role of anti-inflammatory agents in reducing cardiovascular events. Trehalose is a natural disaccharide able to reduce inflammation by enhancing macrophage autophagic activity. This action has been demonstrated to attenuate atherosclerotic plaque development in various pro-atherogenic animal models. However, at present, no data about the efficacy of this compound in human subjects have been published. METHODS: We performed a randomized, double-blind trial involving 15 patients with history of myocardial infarction and evidence of systemic inflammation (defined as C-reactive protein > 2 mg/L). The patients were randomly assigned, in 2:1 ratio, to receive either intravenous trehalose (15 g once weekly) or placebo for 12 weeks. The primary efficacy end-point was the change in arterial wall inflammation, assessed by quantifying 18F-FDG PET/CT uptake in carotid arteries and ascending aorta. RESULTS: The MDS TBR change of the index vessel at 3-month follow-up was not significant in treatment and placebo groups. Furthermore, we could not demonstrate any significant difference between the trehalose group and control group in changes of cIMT from baseline to 3 months in the overall population. No significant changes in echocardiographic measurement were noted after trehalose treatment. Except for the change in urea level in placebo group (31.00 ± 6.59 vs. 25.60 ± 6.402 P = 0.038) no other changes were detected after treatment. Also, there was a significant difference between changes in alanine aminotransferase (ALT) trehalose and placebo groups. CONCLUSION: This was the first study that specifically assessed the effects of intravenous trehalose on atherogenesis in human subjects. Trehalose treatment was characterized by an optimal safety profile, but no significant reduction in arterial wall inflammation could be observed. This might be a consequence of the small sample size of this trial. Larger studies are needed to better assess the efficacy of this compound in this clinical context.

PET NEMA IQ Phantom dataset: image reconstruction settings for quantitative PET imaging.

The data presented here provide information about the role of reconstruction parameters on Positron Emission Tomography (PET) image quantification. Multiple phantom measurements in four different Spheres to Background Ratio (SBR) were performed on Biograph 6 TruePoint TrueV PET/CT scanner. PET raw data were reconstructed with/without resolution recovery algorithm using six various iteration x subsets with five different Full-Width Half-Maximum (FWHM) values of Gaussian post-smoothing filter. The Recovery Coefficient (RC) of six spheres using three common Volume of Interest (VOI) methods (max, 3D-50% Isocontour, and peak) were calculated. Moreover, SUVmax, SUVmean, and SUVpeak and volumetric indices, such as metabolic tumor volume (MTV), volume recovery coefficient (VRC), and total lesion glycolysis (TLG) were measured. RCmax, RC50%, and RCpeak as a function of sphere size were plotted in all reconstruction methods considering different SBRs. The data could be noticeable for standardization and optimization of quantitative metrics in PET imaging.

Physiological distribution of 18F-FDG in the spinal cord: A systematic review.

Context: The importance of physiologic distribution of 18F-FDG in the spinal cord.Objective: The recognition of the physiologic distribution of 18F-FDG in the spinal cord is pivotal for accurate PET/CT imaging interpretation, especially in oncologic patients. Therefore, we performed a systematic review to investigate the normal distribution of 18F-FDG throughout the spinal cord.Methods: Data sources: We carried out a comprehensive search of the literature on the physiologic patterns of 18F-FDG distribution in the spinal cord. PubMed and Scopus databases were searched using the following keywords: "spinal cord" AND "FDG". Data extraction: Findings of the selected articles were described.Results: Thirteen studies comprising 24,125 patients entered the systematic review. These investigations showed discrepancies in location, size, number, and intensity of 18F-FDG uptake throughout the spinal cord. However, cumulative results showed that 18F-FDG uptake was higher in the lower thoracic portion of spinal cord (T11-T12). Moreover, a decreasing trend in 18F-FDG uptake was observed from cervical to lumbar levels. Low maximal standardized uptake values, female sex, and higher body weight seem to be related to the physiological spinal cord 18F-FDG uptake.Conclusions: On 18F-FDG PET/CT imaging, focal hypermetabolism of the spinal cord at the level of lower thoracic and lower cervical vertebrae should be considered physiological until proven otherwise.

Inguino-scrotal bladder hernia: an unexpected finding on 68Ga-PSMA-11 PET/CT.

Bladder herniation is an uncommon condition mimicking suspicious metastasis on PET/CT imaging. We report a 67 y/o man with prostate cancer referred for recurrence evaluation with 68Ga-PSMA-11 PET/CT. The scan showed an asymmetric site of intense tracer accumulation in the left inguino-scrotal region with the same SUVmax to the pelvic bladder. Reviewing cross sectional CT images with PET confirmed the inguino-scrotal bladder herniation.

177Lu-labeled cyclic RGD peptide as an imaging and targeted radionuclide therapeutic agent in non-small cell lung cancer: Biological evaluation and preclinical study.

Non-small cell lung carcinoma (NSCLC) is among the most lethal lung cancers responsible for 80-85% of death. αvß3 integrin receptor subtype has been identified as a lung cancer biomarker since its expression correlates with tumor progression and metastasis. The extracellular domain of the receptor forms a binding site for RGD-based sequences. Therefore, specific targeting of αvß3 integrin receptors by these short peptides can be an excellent candidate for cancer imaging and therapy. In this research, the radiolabeling of DOTA-E(cRGDfK)2 with 177Lu was efficiently implemented. The Log P value, in vivo, in vitro, metabolic stability, cellular uptake and specific binding of the radiopeptide was determined. The tumor targeting capacity and the therapeutic potential of the radiotracer was studied in A549 tumor-bearing mice. Imaging studies at different time intervals were performed by SPECT/CT. Radiochemical purity of more than 99% and Log P of -3.878 was obtained for 177Lu-labelled peptide. Radiotracer showed favorable in vivo, in vitro and metabolic stability. The radiopeptide dissociation constant (Kd) was 15.07 nM. Radiopeptide specific binding was more than 95%. Biodistribution studies showed high accumulation of the radiopeptide in tumor and rapid excretion by urinary route. Maximum tumor uptake was at 4 h post-injection. Following administration of this radiopeptide to mice, not only tumor growth was suppressed, but significant tumor shrinkage was also observed. In conclusion, this radiopeptide can be employed for staging, follow-up imaging and as peptide receptor radionuclide therapeutic agent allowing efficient therapy for NSCLC and other cancers overexpressing αvß3 integrin receptors.

Radiosynthesis, Biological Evaluation, and Preclinical Study of a 68Ga-Labeled Cyclic RGD Peptide as an Early Diagnostic Agent for Overexpressed α v ß 3 Integrin Receptors in Non-Small-Cell Lung Cancer.

The α v ß 3 integrin receptors have high expression on proliferating growing tumor cells of different origins including non-small-cell lung cancer. RGD-containing peptides target the extracellular domain of integrin receptors. This specific targeting makes these short sequences a suitable nominee for theranostic application. DOTA-E(cRGDfK)2 was radiolabeled with 68Ga efficiently. The in vivo and in vitro stability was examined in different buffer systems. Metabolic stability was assessed in mice urine. In vitro specific binding, cellular uptake, and internalization were determined. The tumor-targeting potential of [68Ga]Ga-DOTA-E(cRGDfK)2 in a lung cancer mouse model was studied. Besides, the very early diagnostic potential of the 68Ga-labeled RGD peptide was evaluated. The acquisition and reconstruction of the PET-CT image data were also carried out. Radiochemical and radionuclide purity for [68Ga]Ga-DOTA-E(cRGDfK)2 was >%98 and >%99, respectively. Radiotracer showed high in vivo, in vitro, and metabolic stability which was determined by ITLC. The dissociation constant (K d) of [68Ga]Ga-DOTA-E(cRGDfK)2 was 15.28 nM. On average, more than 95% of the radioactivity was specific binding (internalized + surface-bound) to A549 cells. Biodistribution data showed that radiolabeled peptides were accumulated significantly in A549 tumor and excreted rapidly by the renal system. Tumor uptake peaks were at 1-hour postinjection for [68Ga]Ga-DOTA-E(cRGDfK)2. The tumor was clearly visualized in all images. [68Ga]Ga-DOTA-E(cRGDfK)2 can be used as a peptide-based imaging agent allowing very early detection of different cancers overexpressing α v ß 3 integrin receptors and can be a potential candidate in clinical peptide-based imaging for lung cancer.

Application of [68Ga]PSMA PET/CT in Diagnosis and Management of Prostate Cancer Patients.

PURPOSE: The early and accurate diagnosis of locoregional recurrence or metastasis in prostate cancer (PC) has a significant impact on treatment options. Prostatic-specific membrane antigen (PSMA) positron emission tomography (PET)/x-ray computed tomograph (CT) imaging has recently been introduced as a novel procedure in managing PC. The aim of this study was to evaluate the efficacy of [68Ga]PSMA PET/CT in managing PC patients and to compare the detection rate of PET/CT and bone scans (BSs) in detecting bone metastasis. PROCEDURES: We evaluated 415 patients with PC who underwent [68Ga]PSMA PET/CT between March 2015 and September 2018. The patients were classified into three groups: staging, biomedical recurrence (BCR), and follow-up or monitoring, based on the intent to perform PET/CT. RESULTS: We evaluated 415 patients aged 41-99 (68.25 ± 9.59). Of these patients, 344 (82.9 %) had at least one localized lesion. The detection rates were 48.3 %, 52.6 %, 74.4 %, 79.6 %, and 93.9 % for a PSA value of < 0.2 ng/ml, ≥ 0.2-< 0.5 ng/ml, ≥ 0.5-< 1 ng/ml, ≥ 1-< 2 ng/ml, and ≥ 2 ng/ml, respectively (p < 0.05). The detection rates increased significantly with higher GSs; the rates were 68.3 % (28/41), 74.5 % (73/98), 93.9 % (46/49), and 91 % (61/67) for a GS of < 7, 7, 8, and > 8, respectively (p < 0.05). An ideal cut-off value of > 1.16 ng/ml was obtained for PSA value, which equates to specificity of 75 % and sensitivity of 77 %. In comparing BSs and PET/CT, a region-based analysis showed the superiority of PET/CT over BSs for all regions expect the skull (p < 0.05). PET/CT detected 258 suspicious regions, 255 of which were metastatic and three of which were equivocal. BSs detected only 223 suspicious regions, 203 of which were metastatic and 20 of which were equivocal. CONCLUSIONS: [68Ga]PSMA PET/CT showed a high detection rate for lesions in PC patients. PSA level, GS, and a PSA doubling time of less than 6 months were shown to be the affective variables. In addition, 68Ga-PSMA PET/CT showed better performance in detecting bone lesions than BSs.

18FDG PET/CT in pulmonary arcinosarcoma and rain etastasis.

Carcinosarcoma is a rare type of cancer that is composed of a mixture of sarcomatous and carcinomatous elements. Pulmonary carcinosarcoma has a 25% five-year survival rate with a prognosis poorer than other non-small cell lung carcinomas. Herein, we report a case of pulmonary carcinosarcoma and its 18F-FDG PET/CT findings. A 61-year-old male patient presented with brain symptoms, including headache, nausea, right hemiplegia, and few attacks of seizures. He underwent brain computed tomography (CT) scan showing a brain lesion in the left parietal lobe. The patient underwent excisional biopsy, and brain lesion was removed. The results of tissue sampling were indicative of carcinosarcoma. Based on anatomical imaging and evidence of pulmonary lesion, the patient underwent 18FDG PET/CT that revealed a heterogeneous mass on the upper lobe of the left lung. An intense FDG uptake was observed along the rim of the mass; however, no FDG uptake was observed in the center of the mass. There were multiple mediastinal lymph nodes with a high FDG uptake. Pulmonary carcinosarcoma was confirmed by tissue sampling.

Benign High-Flow Priapism With a Diffuse and Intense 18F-FDG Uptake on 18F-FDG PET/CT Scanning.

We present benign high-flow priapism with intensive F-FDG uptake as an unusual finding in a case of testicular teratocarcinoma with a history of left orchiectomy and chemotherapy. F-FDG PET/CT scan showed pulmonary metastases, left obturator node involvement, and intense F-FDG uptake in the penis. Upon examination, the patient had a painless erection that lasted for couple of days. Because of pulmonary metastases, second-line chemotherapy regimen was started by his physician. The patient's priapism resolved spontaneously, with no episode of recurrence at 2 years' follow-up.

68Ga DOTATATE PET/CT Versus 18F-FDG PET/CT for Detecting Intramedullary Hemangioblastoma in a Patient With Von Hippel-Lindau Disease.

Von Hippel-Lindau disease is an inherited syndrome associated with several benign and malignant tumors such as central nervous system (CNS) hemangioblastoma. Herein, we report a known case of A Von Hippel-Lindau patient with a cerebral hemangioblastoma who was referred for further evaluation because of recent paraparesis. F-FDG PET/CT showed no focal uptake in the thoracic spine, which demonstrated increased Ga DOTATATE activity, owing to overexpression of somatostatin receptors, suggesting spinal cord hemangioblastoma. This case report indicates the significant role of Ga-labeled somatostatin receptor analogs in the diagnosis of hemangioblastoma.