Κυριακή 6 Ιουνίου 2021

Correlation between tumor infiltrating immune cells and peripheral regulatory T cell determined using methylation analyses and its prognostic significance in resected gastric cancer

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by Koung Jin Suh, Jin Won Kim, Ji Eun Kim, Ji Hea Sung, Jiwon Koh, Kui-Jin Kim, Ji-Won Kim, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee, Keun-Wook Lee

Peripheral regulatory T cells (pTregs) are a highly immunosuppressive fraction of CD4+ T cells. We aimed to evaluate the clinical significance of pTregs in patients with gastric cancer and to determine the correlation between pTregs and immune cell infiltration in tumor microenvironment. pTregs status was determined by assessing the pTreg/total T-cell ratio (ratio of Foxp3 Treg-specific demethylated region (TSDR) to CD3G/CD3D demethylation, so-called Cellular Ratio of Immune Tolerance "ImmunoCRIT") using methylation analyses in 433 patients with gastric cancer who received curative surgery. Among 422 evaluable patients, 230 (54.5%) had high ImmunoCRIT (> 21.0). Patients with high ImmunoCRIT had significantly shorter disease-free survival (DFS) and overall survival (OS) than those with high ImmunoCRIT (p = 0.030, p = 0.008, respectively). In multivariate analysis, high ImmunoCRIT kept a prognostic role for shorter OS (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.4–2.9; p = 0.005). CD3+ cell density and CD4+ cell density was significantly higher within the tumor in high ImmunoCRIT group than those in low ImmunoCRIT group (CD3+ cell, 202.12/mm2 vs. 172.2/mm2, p = 0.029; CD4+ cell, 56.5/mm2 vs. 43.5/mm2, p = 0.007). In conclusion, the peripheral ImmunoCRIT determined by epigenetic methylation analysis provides prognostic information in resected gastric tumors.
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Pharmacokinetic Modeling of 18F-FDOPA PET in the Human Brain for Early Parkinson's Disease

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):69-78. doi: 10.4274/mirt.galenos.2021.08831.

ABSTRACT

OBJECTIVES: Early detection is essential for the treatment approaches of Parkinson's disease (PD). Clinical criteria alone may be insufficient to distinguish early PD from other conditions. This study aimed to investigate the transfer rate constants of 6-18F-fluoro-L-dopa (18F-FDOPA) in positron emission tomography (PET) brain images as a sensitive parameter to detect early PD.

METHODS: Retrospective 18F-FDOPA PET data of five patients with early PD were collected. PET data were acquired for 90 min after intravenous injection of 306-379 MBq 18F-FDOPA, and reconstructed into a series of 18 five-minute frames. Reoriented PET images were coregistered and normalized with the PET brain template on the statistical parametric mapping. The 18F-FDOPA activity concentrations were measured in the striatum, caudate, and putamen on both sides: Contralateral (as PD) and ipsilateral (as control) to the main motor symptoms. The pharmacokinetic model was generated using the SAAM II simulation software. The transfer rate constants across the blood-brain barrier (forward, K1 and reverse, k2) and decarboxylation rate constants (k3) were estimated in these regions.

RESULTS: The activity uptakes in the contralateral striatum (0.0323%±0.0091%) and putamen (0.0169%±0.0054%) were significantly lower than the control (0.0353%±0.0086%, 0.0199%±0.0054%, respectively). The K1 and k3 were significantly lower in the contralateral striatum and putamen (p<0.05). There were no significant differences in any transfer rate constants in the caudate.

CONCLUSION: The transfer rate constants (K1 and k3) of 18F-FDOPA on the contralateral striatum and putamen were significantly lower than the control. These biokinetic data could be potential indicators for quantitative detection of early PD diagnosis.

PMID:34082499 | DOI:10.4274/mirt.galenos.2021.08831

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68Ga-PSMA PET/CT Versus 18F-FDG PET/CT for Imaging of Hepatocellular Carcinoma

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):79-85. doi: 10.4274/mirt.galenos.2021.92053.

ABSTRACT

OBJECTIVES: This study aimed to compare the metabolic parameters obtained from 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and gallium-68 (68Ga)-prostate-specific membrane antigen (PSMA) PET/CT and investigate the relationship between serum alpha-fetoprotein and PET scan parameters in patients with hepatocellular carcinoma.

METHODS: Fourteen patients were recruited after dynamic magnetic resonance imaging (MRI) of the upper abdomen, and 18F-FDG and 68Ga-PSMA PET/CT imaging studies were conducted. Regions of interest (ROIs) were drawn from lesion-free liver tissue, abdominal aorta (A), and right medial gluteal muscle (G) for the background activity. Maximum standard uptake value (SUVmax) of these regions were compar ed with the SUVmax of primary tumor (T).

RESULTS: On visual assessment, five patients (36%) experienced low 18F-FDG uptake in the primary lesion, three patients (21%) experienced moderate uptake, and six patients (43%) experienced high uptake. However, only one patient (7%) showed low 68Ga-PSMA uptake, two patients (14%) showed moderate uptake, and 11 patients (79%) showed high uptake. Four patients with a low 18F-FDG uptake showed high 68Ga-PSMA uptake, while one patient exhibited low uptake with both 18F-FDG and 68Ga-PSMA. The number of lesions on 68Ga-PSMA PET/CT and MRI was significantly higher than 18F-FDG PET/CT (p=0.042 and 0.026, respectively). T/A and T/G values were significantly higher in 68Ga-PSMA than 18F-FDG (p=0.002 and 0.002, respectively).

CONCLUSION: 68Ga-PSMA PET/CT is superior to 18F-FDG PET/CT in the staging o f hepatocellular carcinoma. High 68Ga-PSMA uptake could be promising for PSMA-targeted radionuclide treatments.

PMID:34082503 | DOI:10.4274/mirt.galenos.2021.92053

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Oncological Follow-up with 2-[18F]-FDG PET/CT in Li-Fraumeni Syndrome

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):110-112. doi: 10.4274/mirt.galenos.2020.33255.

ABSTRACT

Li-Fraumeni syndrome is a rare disorder caused by abnormalities of the tumor-suppressor protein P53 gene. We present the case of a 26-years-old female diagnosed with bilateral ductal carcinoma. The genetic panel for breast cancer gene 1 (BRCA1) and BRCA2 mutations was negative and positive heterozygous germline tumor protein P53 gene mutations, considering Li-Fraumeni syndrome. A 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) was used for postsurgical staging to show the right lung hypermetabolic nodule. A lobectomy was accomplished, and histopathology reported pulmonary adenocarcinoma. A year later, oncological follow-up was conducted with 2-[18F]-FDG PET/CT without evidence of abnormalities.

PMID:34082513 | DOI:10.4274/mirt.galenos.2020.33255

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Correlation of 18F-FDG/PET SUVmax, SUVmean, MTV, and TLG with HIF-1α in Patients with Colorectal Cancer

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):93-100. doi: 10.4274/mirt.galenos.2021.04934.

ABSTRACT

OBJECTIVES: Post-hypoxia hypoxia-inducible factor (HIF)-1α activation plays a vital role in colorectal cancer (CRC) angiogenesis. Although glucose metabolism is induced in some cancer types via HIF-1α, the prognostic significance of HIF-1α in CRC and its correlation with 18fluorinefluorodeoxyglucose (18F-FDG) uptake in positron emission tomography (PET) remain controversial. This study aims to investigate the association between 18F-FDG/PET parameters and HIF-1α expression in CRC.

METHODS: Thirty-six histopathologically confirmed patients with CRC who had 18F-FDG/PET scans before surgery were enrolled in the study. The correlations between the maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), total lesion glycolysis, HIF-1α overe xpression, and histopathological features were evaluated.

RESULTS: The tumor location, tumor diameter, perineural invasion, lymphovascular invasion, T and N stage were not significantly correlated with HIF-1α overexpression. In contrast, the tumor differentiation was negatively correlated with HIF-1α expression (r=-0.332, p=0.048). None of the 18F-FDG/PET parameters was significantly correlated with HIF-1α overexpression. A significant relationship was found between tumor differentiation, tumor necrosis percentage, and MTV (p=0.030, p=0.020).

CONCLUSION: The expected association between HIF-1α overexpression and 18F-FDG/PET parameters was not found in this study. However, there was a relationship between MTV, tumor differentiation, and tumor necrosis percentage. Hence, further studies are required to predict the pathological and prognostic courses of CRC using a diagnostic 18F-FDG/PET evaluation.

PMID:34082509 | DOI:10.4274/mirt.galenos.2021.04934

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Incidental Skeletal Findings on Sodium-fluoride Positron Emission Tomography: A Collection of Benign Tumors

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):113-116. doi: 10.4274/mirt.galenos.2020.89266.

ABSTRACT

Sodium-fluoride (NaF) positron emission tomography (PET) is a sensitive method to detect altered bone mineralization. Its increasing use in routine clinical practice for metastatic bone disease has also resulted in the detection or characterization of incidental benign bone lesions. A spectrum of NaF PET scan cases with benign bone tumors are presented in this article, including whole body PET bone scan and selected PET/computed tomography (CT), CT, or magnetic resonance imaging (MRI) of the region of interest. The reader will be able to improve their knowledge related to the clinical presentation of these entities, some are rare and recognize based on NaF PET and CT/MRI patterns by reviewing these cases.

PMID:34082514 | DOI:10.4274/mirt.galenos.2020.89266

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Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Case of Concurrent Neuroendocrine Tumors and Meningioma: Achieving Two Things in a Single Action

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):107-109. doi: 10.4274/mirt.galenos.2020.69783.

ABSTRACT

We present a partial response of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in a case of concurrent neuroendocrine tumors (NETs) and meningioma. In addition to the valuable role of PRRT in inoperable NETs, it has been demonstrated that this treatment can be a promising therapy for progressive meningioma, especially in patients with low grade and refractory to standard regime.

PMID:34082512 | DOI:10.4274/mi rt.galenos.2020.69783

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PET/CT Findings of a Patient with Striped Muscle Metastasis of Invasive Breast Carcinoma

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):117-118. doi: 10.4274/mirt.galenos.2020.90377.

ABSTRACT

A 37-year-old female with a history of invasive breast carcinoma was referred to our department for an 18flor-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography whole-body scan. An intense 18F-FDG uptake in striped muscles anterior to the left thigh region was noted. Excisional biopsy outcome from the left vastus medialis muscle was found to be consistent with striped muscle metastasis from breast carcinoma.

PMID:34082515 | DOI:10.4274/mirt.galenos.2020.90377

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The Role of Metabolic Volumetric Parameters in Predicting Malignancy in Incidental Thyroid Nodules Detected in 18F-FDG PET/CT Scans

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):86-92. doi: 10.4274/mirt.galenos.2021.75983.

ABSTRACT

OBJECTIVES: The metabolic activities of tumors can be calculated volumetrically during positron emission tomography/computed tomography (PET/CT) imaging using metabolic tumor volume (MTV) and total lesion glycolysis (TLG). This study aimed to evaluate the roles of MTV and TLG in predicting the malignancy risk of incidental thyroid nodules detected by PET/CT imaging.

METHODS: Active metabolic areas of each section were manually drawn by region of interest to calculate the MTV of nodules, and all obtained values were then summed. TLG, the product of mean standardized uptake value and MTV, was calculated by multiplying two values. All participants underwent thyroid ultrasonography imaging. All nodules were divided into risk classes according to the European Thyroid Image Reporting and Data System (EU-TIRADS) that was developed by the E uropean Thyroid Association. The American Thyroid Association Guidelines were used to determine which thyroid nodules would undergo thyroid fine-needle biopsy (FNAB). Results were classified according to the Bethesda scoring system.

RESULTS: TLG levels were significantly higher in malignant or malignant-suspicious nodules than in benign nodules (p=0.013). Although MTV levels were high in malignant or malignant-suspicious nodules than in benign and non-diagnostic nodules, it was statistically insignificant at limit values (p=0.079). Areas under curve (AUC) were 0.726 (p=0.005) and AUC: 0.668 (p=0.039) for TLG and MTV, respectively. The 2.3 g cut-off value of TLG has a sensitivity of 85.7% and specificity of 59.0%. The 1.7 mL cut-off value of MTV has a sensitivity of 78.6% and specificity of 60.4%.

CONCLUSION: We believe that TLG evaluation will be useful in predicting high-risk malignancy or malignancy suspicion based on EU-TIRADS risk classification of incidental thyroid nodules detected in PET/CT images. We believe that unnecessary thyroid FNABs can be avoided for thyroid incidental nodules if such relation and cut-off values are determined and that it will be useful in hastening the operation of the necessary patients.

PMID:34082507 | DOI:10.4274/mirt.galenos.2021.75983

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18F-FDG PET/CT Imaging in an Unusual Case of Cutaneous Melanoma Arising From Congenital Melanocytic Nevus in a Two-year-old Girl

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):119-121. doi: 10.4274/mirt.galenos.2020.48278.

ABSTRACT

Childhood malignant melanoma (MM) is extremely uncommon. We report an unusual case of cutaneous melanoma that developed from a medium-sized congenital melanocytic nevus (CMN) in a two-year-old girl. The patient had a history of CMN on the right hip, and she presented with a new ulcerative area with irregular borders and bleeding on CMN. Histopathological examination of the nevus revealed a MM. 18Florfluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography was performed for metastatic evaluation. The scan demonstrated metastatic increased 18F-FDG uptake in the right external iliac and inguinal lymph nodes.

PMID:34082516 | DOI:10.4274/mirt.galenos.2020.48278

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Systemic Sarcoidosis Induced by Chemotherapy, Mimicking Metastatic Testicular Carcinoma with 18F-FDG PET/CT

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Mol Imaging Radionucl Ther. 2021 Jun 3;30(2):126-128. doi: 10.4274/mirt.galenos.2020.51422.

ABSTRACT

A 34-year-old male patient who had left orchiectomy and received three cycles of chemotherapy for testicular mix germ cell carcinoma was referred for 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for complaints of weight loss and fever. PET/CT showed multiple and progressive 18F-FDG uptakes in supra and infra diaphragmatic lymphatic regions, and multiple abnormal 18F-FDG uptakes were noted in the lytic formed skeletal lesions. Clinicians remain in doubt regarding the multiple metastatic lesions without elevated serum tumor marker levels (alpha-fetoprotein, beta-human chorionic gonadotrophin, CA19-9, and carcinoembryonic antigen). Biopsy of the lytic lesion in the iliac bone revealed granulomatous inflammation suggestive of sarcoidosis. System ic prednisone at 20-40 mg/daily was started. 18F-FDG PET/CT images showed complete metabolic response to prednisone 8 months following the start of treatment.

PMID:34082518 | DOI:10.4274/mirt.galenos.2020.51422

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