Paediatric metastatic ganglioneuroblastoma on 68Ga-DOTA NOC PET-CT.

68Ga-DOTA NOC PET-CT imaging has been shown to have high accuracy for the evaluation of neuroendocrine tumours. We report a case of a 3-year-old boy who presented with a right paravertebral soft tissue mass. Biopsy showed ganglioneuroblastoma. The patient was referred for 68Ga-DOTA NOC for staging. 68Ga-DOTA NOC PET/CT images showed somatostatin-avid large right paravertebral soft tissue mass representing the primary lesion, along with increased radiotracer localization at multiple metastatic lytic bone lesions in the axial and appendicular skeleton. 68Ga-DOTA NOC PET-CT is helpful in the evaluation of the disease extent of neuroendocrine tumours including ganglioneuroblastoma.

Phantom and clinical evaluation of the effect of a new Bayesian penalized likelihood reconstruction algorithm (HYPER Iterative) on 68Ga-DOTA-NOC PET/CT image quality.

BACKGROUND: Bayesian penalized likelihood (BPL) algorithm is an effective way to suppress noise in the process of positron emission tomography (PET) image reconstruction by incorporating a smooth penalty. The strength of the smooth penalty is controlled by the penalization factor. The aim was to investigate the impact of different penalization factors and acquisition times in a new BPL algorithm, HYPER Iterative, on the quality of 68Ga-DOTA-NOC PET/CT images. A phantom and 25 patients with neuroendocrine neoplasms who underwent 68Ga-DOTA-NOC PET/CT were included. The PET data were acquired in a list-mode with a digital PET/CT scanner and reconstructed by ordered subset expectation maximization (OSEM) and the HYPER Iterative algorithm with seven penalization factors between 0.03 and 0.5 for acquisitions of 2 and 3 min per bed position (m/b), both including time-of-flight and point of spread function recovery. The contrast recovery (CR), background variability (BV) and radioactivity concentration ratio (RCR) of the phantom; The SUVmean and coefficient of variation (CV) of the liver; and the SUVmax of the lesions were measured. Image quality was rated by two radiologists using a five-point Likert scale. RESULTS: The CR, BV, and RCR decreased with increasing penalization factors for four "hot" spheres, and the HYPER Iterative 2 m/b groups with penalization factors of 0.07 to 0.2 had equivalent CR and superior BV performance compared to the OSEM 3 m/b group. The liver SUVmean values were approximately equal in all reconstruction groups (range 5.95-5.97), and the liver CVs of the HYPER Iterative 2 m/b and 3 m/b groups with the penalization factors of 0.1 to 0.2 were equivalent to those of the OSEM 3 m/b group (p = 0.113-0.711 and p = 0.079-0.287, respectively), while the lesion SUVmax significantly increased by 19-22% and 25%, respectively (all p < 0.001). The highest qualitative score was attained at a penalization factor of 0.2 for the HYPER Iterative 2 m/b group (3.20 ± 0.52) and 3 m/b group (3.70 ± 0.36); those scores were comparable to or greater than that of the OSEM 3 m/b group (3.09 ± 0.36, p = 0.388 and p < 0.001, respectively). CONCLUSIONS: The HYPER Iterative algorithm with a penalization factor of 0.2 resulted in higher lesion contrast and lower image noise than OSEM for 68Ga-DOTA-NOC PET/CT, allowing the same image quality to be achieved with less injected radioactivity and a shorter acquisition time.

A Very Unusual Pattern of Intraperitoneal and Extraperitoneal Heterotropic Splenic Tissue-Mimicking Metastases Identified on 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and 99mTc Heat-denatured Erythrocyte Study.

The dissemination and autotransplantation of viable splenic tissue in different anatomic compartments of the body can present a diagnostic dilemma, especially when metastatic disease is suspected. We report a case of a 30-year-old male with well-differentiated gastric neuroendocrine tumor (Grade II) treated with surgery. Follow-up 68Ga-DOTA-NOC demonstrated a suspicious peritoneal soft-tissue nodule in the right paracolic gutter with increased tracer uptake. In view of splenectomy 10 years ago, the patient underwent 99mTc heat-denatured erythrocyte study which showed a very unusual pattern of multiple tracer-avid foci of splenic tissue in both intraperitoneal and extraperitoneal distributions. The integration of the patient's history and complementary nuclear imaging results led to the correct diagnosis of splenosis.

Utilidad de la tomografía por emisión de positrones/ tomografía computada (PET/CT) en pacientes con diagnóstico de meduloblastoma / Usefulness of Positron Emission Tomography/Computed Tomography (PET/CT) in Patients Diagnosed with Medulloblastoma

Resumen: La tomografía por emisión de positrones/tomografía computada (PET/CT) por sus siglas en inglés, es una modalidad de imagen única que proporciona evidencia in vivo de actividades tanto bioquímicas como fisiológicas en diferentes órganos y estructuras del cuerpo. El meduloblastoma es el tumor maligno más frecuente del sistema nervioso central (SNC) en pacientes pediátricos, por este motivo el PET/CT juega un papel importante en el manejo de estos pacientes ya que proporciona información sobre el grado y extensión del tumor, así como a determinar el sitio adecuado para la toma de biopsia, valorar la respuesta al tratamiento y determinar el pronóstico del paciente. Existen diferentes radiofármacos para la evaluación de los tumores de sistema nervioso central, pero se ha estudiado que el 18F-FDG (flúor-2-fluoro-2-desoxi-D-glucosa) y el 68Ga-DOTA-NOC (68Ga-DOTA0-1NaI3-octreotide) nos ayudan a evaluar y dar seguimiento a pacientes con diagnóstico de meduloblastoma. El meduloblastoma tiene una sobreexpresión de transportadores de glucosa, principalmente tipo 1 y sobreexpresión de receptores de somatostatina predominantemente tipo 2, lo cual permite que exista una gran afinidad por estos radiofármacos.

Abstract: PET/CT (positron emission tomography/computed tomography, for its acronym in English) is a unique imaging method that provides in vivo evidence of both biochemical and physiological activities of the brain, spinal cord and tumors that involve these structures. Medulloblastoma is the most common malignant tumor of the central nervous system (CNS) in pediatric patients, so PET/CT plays an important role as it provides information on the grade and extent of the tumor, as well as to determine the appropriate site for the biopsy, assessing the response to the treatment and the patient's prognosis. There are different radiopharmaceuticals for the evaluation of central nervous system tumors, but 18F FDG (Fluor-2-fluoro-2-desoxy-D-glucose) and 68Ga-DOTA-NOC (68Ga-DOTA0-1NaI3-octreotide) have been studied to help us evaluate and follow up patients diagnosed with medulloblastoma. Medulloblastoma has an overexpression of glucose transporters, mainly type 1, and an overexpression of predominantly type 2 somatostatin receptors, which allows a high affinity for these radiopharmaceuticals.

Evaluation of [68Ga]Ga-DATA-TOC for imaging of neuroendocrine tumours: comparison with [68Ga]Ga-DOTA-NOC PET/CT.

PURPOSE: Recently, the new hybrid chelator DATA (6-amino-1,4-diazepine-triacetate) has been introduced, which has the advantage of high yield and radiolabelling of DATA-based octreotide derivative (TOC) at room temperature in contrast to tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) that needs 95 °C for effective labelling. However, the diagnostic potential of DATA-TOC has not been studied with other chelators in humans. The aim of this study was to compare the diagnostic efficacy of [68Ga]Ga-DATA-TOC with [68Ga]Ga-DOTA-NOC (which is the current standard for imaging neuroendocrine tumours (NET)) in patients of gastroenteropancreatic neuroendocrine tumours (GEP-NETs). METHODS: Fifty patients (thirty-one males and nineteen females) with biopsy-proven GEP-NETs were included in the study. Patients age ranged from 14 to 75 years (mean 46.11 years). All patients underwent two PET studies with [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC. Images were evaluated visually and semi-quantitatively using maximum standardized uptake values (SUVmax) of tumour, mediastinum and liver. Tumour-to-liver (T/L) and tumour-to-mediastinum (T/M) SUVmax ratios were computed. For the purpose of comparison, patient-wise as well as lesion-wise analysis was carried out. The nonparametric-related samples Wilcoxon signed-rank test was used for comparison of the SUVmax values and ratios. RESULTS: On visual evaluation, the biodistribution and image quality of [68Ga]Ga-DATA-TOC was similar to [68Ga]Ga-DOTA-NOC. Physiological liver uptake was lower in [68Ga]Ga-DATA-TOC as compared with [68Ga]Ga-DOTA-NOC, 7.65 ± 5.37 vs 8.94 ± 5.95 (p = 0.009), respectively. On a patient-wise analysis, both [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC were lesion-positive in the 44 patients (88%) and were negative in the 6 patients (12%). On a lesion-based analysis, [68Ga]Ga-DATA-TOC had 98.6% concordance with [68Ga]Ga-DOTA-NOC (232 out of 235 lesions detected). The target tumour SUVmax on [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC were 36.63 ± 32.24 and 40.82 ± 36.89, respectively (p = 0.097). The T/L SUVmax ratios were not significantly different (5.99 ± 5.52 vs 5.67 ± 4.96, p = 0.77). CONCLUSION: [68Ga]Ga-DATA-TOC PET/CT imaging produced results that were comparable with [68Ga]Ga-DOTA-NOC. It, thus, has potential utility as an effective and safe alternative to 68Ga-DOTA-NOC with the added benefit of ease, cost-effective and improved yield of instant kit-type synthesis.

Novel Functional Imaging of Neuroendocrine Tumors.

Somatostatin receptor imaging constitutes an integral part in neuroendocrine tumor visualization and should, because of its vastly superior performance, use 68Ga-DOTA-somatostatin analogue-PET/computed tomography rather than scintigraphy; it is particularly valuable for detecting metastases to lymph nodes, bone, peritoneum, and liver, which may be missed by morphologic imaging. 18FDG-PET/computed tomography is better suited for G3 and high-G2 neuroendocrine tumors. 18FDG-PET/computed tomography provides prognostic information. Alternative available PET tracers are 18F-DOPA and 11C-5-hydroxytryptophan. To take full advantage of the technique PET/computed tomography should include diagnostic intravenous contrast-enhanced computed tomography. PET/MRI is currently mainly investigational.

Correlation between Standardized Uptake Value of 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and Pathological Classification of Neuroendocrine Tumors.

The aim of our study was to correlate tumor uptake of 68Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUVmax) and averaged SUV SUVmean of "main tumor lesions" were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 <2, intermediate grade: Ki-67 3-20, and high grade: Ki-67 >20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUVmax of tumor and Ki-67 index (r = -0.241) and negatively poor agreement between SUVmean of tumor and Ki-67 index (r = -0.094). SUVmax of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUVmean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUVmax and SUVmean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68Ga-DOTA-NOC may be associated with aggressive behavior and may, therefore, result in poor prognosis.

Prognostic Value of 68Ga-DOTANOC PET/CT SUVmax in Patients with Neuroendocrine Tumors of the Pancreas.

UNLABELLED: This study was performed to investigate the role of (68)Ga-DOTANOC SUVmax as a potential prognostic factor in patients with pancreatic neuroendocrine tumor (pNET). METHODS: Among the patients who underwent (68)Ga-DOTANOC PET/CT, we retrospectively collected the data of those who had G1 or G2 pNET (2010 World Health Organization classification), presented with disease on PET/CT and CT, and had at least 6 mo of follow-up. Patients with multiple endocrine neoplasia were excluded. RESULTS: Overall, 43 patients were included. No significant differences in SUVmax were observed with respect to sex, tumor syndrome, stage, World Health Organization classification, or Ki-67. During follow-up (median, 20 mo), 11 patients (35.6%; median, 33 mo; interquartile range, 20-48 mo) had stable disease and 32 (74.4%; median, 19 mo; interquartile range, 14-26 mo) had progressive disease. SUVmax at 24 mo of follow-up was significantly higher (P = 0.022) in patients with stable disease than in patients with progressive disease. The best SUVmax cutoff ranged from 37.8 to 38.0. The major risk factors for progression included an SUVmax of no more than 37.8 (hazard ratio, 3.09; P = 0.003), a Ki-67 of more than 5% (hazard ratio, 2.89; P = 0.009), and medical therapy alone (hazard ratio, 2.36; P = 0.018). Advanced stage (IV) (P = 0.026), an SUVmax of less than 37.8 (P = 0.043), and medical therapy alone (P = 0.015) were also confirmed at multivariate analysis. Median progression-free survival was 23 mo. Significant differences in progression-free survival were observed in relationship to Ki-67 (median, 45 mo for Ki-67 ≤ 5% and 20 mo for Ki-67 > 5%; P = 0.005), SUVmax (<37.8 vs. >38.0: 16.0 vs. 27.0 mo; P = 0.002), and type of therapy (medical vs. peptide receptor radionuclide therapy: 16.0 vs. 26.0 mo; P = 0.014). CONCLUSION: (68)Ga-DOTANOC SUVmax is a relevant prognostic factor in patients with G1 and G2 pNET, and its routine use will improve disease characterization and management in these patients, who may present with atypical cases showing heterogeneous clinical behavior.

Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.

OBJECTIVE: Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. MATERIALS AND METHODS: One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. RESULTS: Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. CONCLUSION: Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.

Dual tracer functional characterization of metastatic gastric carcinoid.

Because of the increasing clinical importance of gastric carcinoids and the difficulty in diagnosing them, the need for non-invasive diagnostic methods is growing. Currently, the only reliable method is upper gastrointestinal endoscopy with biopsy. We report the case of a 32-year-old male where a combination of functional imaging studies ((18)F-fluorodeoxyglucose-positron emission tomography/computed tomography [PET/CT] and (68)Ga-DOTA-NOC PET/CT) not only helped in the correct staging, but also highlighted certain important biological aspects of these tumors, which are important from the management point of view and can prognosticate the patients.