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BACKGROUND: In the present study, we investigated the value of 18F-fibroblast-activation protein inhibitor (FAPI) positron emission tomography/computed tomography (18F-FAPI-42 PET/CT) to preoperative evaluations of appendiceal neoplasms and management for patients. METHODS: This single-center retrospective clinical study, including 16 untreated and 6 treated patients, was performed from January 2022 to May 2023 at Southern Medical University Nanfang Hospital. Histopathologic examination and imaging follow-up served as the reference standard. 18F-FAPI-42 PET/CT was compared to 18F-fluorodeoxyglucose (18F-FDG) PET/CT and contrast-enhanced CT (CE-CT) in terms of maximal standardized uptake value (SUVmax), diagnostic efficacy and impact on treatment decisions. RESULTS: The accurate detection of primary tumors and peritoneal metastases were improved from 28.6% (4/14) and 50% (8/16) for CE-CT, and 43.8% (7/16) and 85.0% (17/20) for 18F-FDG PET/CT, to 87.5% (14/16) and 100% (20/20) for 18F-FAPI-42 PET/CT. Compared to 18F-FDG PET/CT, 18F-FAPI-42 PET/CT detected more regions infiltrated by peritoneal metastases (108 vs. 43), thus produced a higher peritoneal cancer index (PCI) score (median PCI: 12 vs. 5, P < 0.01). 18F-FAPI-42 PET/CT changed the intended treatment plans in 35.7% (5/14) of patients compared to CE-CT and 25% (4/16) of patients compared to 18F-FDG PET/CT but did not improve the management of patients with recurrent tumors. CONCLUSIONS: The present study revealed that 18F-FAPI-42 PET/CT can supplement CE-CT and 18F-FDG PET/CT to provide a more accurate detection of appendiceal neoplasms and improved treatment decision making for patients.
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Neoplasias del Apéndice , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias del Apéndice/diagnóstico por imagen , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Anciano , Adulto , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: This study is performed to investigate the imaging characteristics of the International Association for the Study of Lung Cancer grade 3 invasive adenocarcinoma (IAC) on PET/CT and the value of PET/CT for preoperative predicting this tumor. MATERIALS AND METHODS: We retrospectively enrolled patients with IAC from August 2015 to September 2022. The clinical characteristics, serum tumor markers, and PET/CT features were analyzed. T test, Mann-Whitney U test, χ 2 test, Logistic regression analysis, and receiver operating characteristic analysis were used to predict grade 3 tumor and evaluate the prediction effectiveness. RESULTS: Grade 3 tumors had a significantly higher maximum standardized uptake value (SUV max ) and consolidation-tumor-ratio (CTR) ( P â <â 0.001), while Grade 1 - 2 tumors were prone to present with air bronchogram sign or vacuole sign ( P â <â 0.001). A stepwise logistic regression analysis revealed that smoking history, CEA, SUV max , air bronchogram sign or vacuole sign and CTR were useful predictors for Grade 3 tumors. The established prediction model based on the above 5 parameters generated a high AUC (0.869) and negative predictive value (0.919), respectively. CONCLUSION: Our study demonstrates that grade 3 IAC has a unique PET/CT imaging feature. The prognostication model established with smoking history, CEA, SUV max , air bronchogram sign or vacuole sign and CTR can effectively predict grade 3 tumors before the operation.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Radiofármacos , Estudios Retrospectivos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patologíaAsunto(s)
Neoplasias Cardíacas , Leiomiomatosis , Neoplasias Uterinas , Enfermedades Vasculares , Humanos , Femenino , Leiomiomatosis/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Vena Cava Inferior/diagnóstico por imagen , Atrios Cardíacos/diagnóstico por imagen , Neoplasias Cardíacas/diagnóstico por imagenRESUMEN
OBJECTIVE: In this study, the potential advantage of FAPI over 18 F-labelled deoxyglucose ( 18 F-FDG) in evaluation of the initial staging colorectal cancer (CRC) was investigated. MATERIALS AND METHODS: Thirty-two patients with histopathologically confirmed primary CRC were included in our study. They all underwent both 18 F-FDG and FAPI PET/CT. Lesion detectability and tracer uptakes, mainly quantified by maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR), were compared for paired lesions between both modalities using the Wilcoxon signed-rank test and paired t-test. RESULTS: Thirty-five CRC lesions in 32 patients were diagnosed. The sensitivity of FAPI PET/CT in diagnosis of the CRC lesions was 100% while 93.8% of 18 F-FDG PET/CT. FAPI and 18 F-FDG had a similar uptake in CRC lesion (mean SUVmax: 14.3â ±â 8.6 vs. 15.4â ±â 9.8, P â =â 0.604), but lesions contained mucus and/or signet-ring cell carcinoma seemed to have a trend of higher FAPI uptake although there was no statistical difference (mean SUVmax: 12.7â ±â 5.6 vs. 8.5â ±â 4.1, P â =â 0.152) and higher TBR (13.4â ±â 6.2 vs. 4.9â ±â 2.2, P â =â 0.004) than those of 18 F-FDG. For regional lymph node metastases, both FAPI and FDG PET/CTs showed high sensitivity (7/8 vs. 7/8), specificity (7/8 vs. 6/8) and accuracy (14/16 vs. 13/16) (all P â >â 0.05). For distant metastasis, FAPI PET/CT depicted more positive lesions in distant lymph node (46 vs. 26), liver (13 vs. 7) and peritoneum (107 vs. 45) than 18 F-FDG PET/CT. FAPI PET/CT also had a higher peritoneal cancer index score (median 11 vs 4; P â <â 0.001) than 18 F-FDG PET/CT in evaluation of peritoneal metastases. CONCLUSION: FAPI PET/CT showed high sensitivity in detection of primary CRC and superiority to 18 F-FDG PET/CT in detection of metastases to distant lymph node, liver and peritoneum.
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Neoplasias Colorrectales , Quinolinas , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Neoplasias Colorrectales/diagnóstico por imagen , Fibroblastos , Radioisótopos de GalioRESUMEN
ABSTRACT: A 49-year-old woman was referred to our hospital due to suspected lung metastases for 1 month. She had a history of thyroid micropapillary carcinoma and uterine leiomyomas. An 18 F-FDG PET/CT scan, which was performed to search the source of the presumed metastasis of the disease, showed multiple lung metastases and 2 18 F-FDG-avid foci in the thyroid and colon. Biopsy of lung and resection of colon lesions were then performed, and the disease was finally identified to be rare primary colon leiomyosarcoma with multiple lung metastases.
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Neoplasias del Colon , Leiomiosarcoma , Neoplasias Pulmonares , Femenino , Humanos , Persona de Mediana Edad , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Leiomiosarcoma/diagnóstico por imagen , Radiofármacos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias del Colon/diagnóstico por imagenAsunto(s)
Melanoma , Vena Cava Inferior , Humanos , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Melanoma/diagnóstico por imagen , Melanoma/patologíaRESUMEN
6-O-[18F]Fluoroethylerlotinib (6-O-[18F]FEE), with a suitable half-life for commercial distribution, may be a good replacement for [11C]erlotinib to identify epidermal growth factor receptor (EGFR) positive tumors with activating mutations to tyrosine kinase inhibitors therapy. In this study, we explored the fully automated synthesis of 6-O-[18F]FEE and investigated its pharmacokinetics in tumor-bearing mice. 6-O-[18F]FEE with high specific activity (28-100 GBq/µmol) and radiochemistry purity (over 99 %) was obtained by two-step reaction and Radio-HPLC separation in PET-MF-2 V-IT-1 automated synthesizer. PET imaging of 6-O-[18F]FEE in HCC827, A431, and U87 tumor-bearing mice with different EGFR expression and mutation was performed. Uptake and blocking of PET imaging indicated that the probe specifically targeted exon 19 deleted EGFR (the quantitative analysis of tumor-to-mouse ratio for HCC827, HCC827 blocking, U87, A431 was 2.58 ± 0.24, 1.20 ± 0.15, 1.18 ± 0.19, and 1.05 ± 0.13 respectively). Dynamic imaging was used to study the pharmacokinetics of the probe in tumor-bearing mice. Logan plot graphical analysis demonstrated late linearity and a high fitting correlation coefficient (0.998), supporting reversible kinetics. According to the Akaike Information Criterion (AIC) rule, the 2-compartment reversible model was more consistent with the metabolic properties of 6-O-[18F]FEE. The automated radiosynthesis and pharmacokinetic analysis will promote clinically transformation of 6-O-[18F]FEE.
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Neoplasias Pulmonares , Tomografía de Emisión de Positrones , Animales , Ratones , Clorhidrato de Erlotinib , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Receptores ErbB , Mutación , Línea Celular TumoralRESUMEN
ABSTRACT: Chromophobe renal cell carcinoma (RCC) is a rare tumor. We described findings of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT of metastatic chromophobe RCC in a 56-year-old woman. 68Ga-FAPI-04 PET/CT demonstrated that the metastatic lesions in the liver, left posterior abdominal wall, and the left waist had intense uptake of 68Ga-FAPI-04, which was higher than that of 18F-FDG on 18F-FDG PET/CT. 68Ga-FAPI-04 PET/CT also delineated the metastatic lesions more clearly than 18F-FDG PET/CT. This case highlights 68Ga-FAPI-04 PET/CT may be promising in restaging of chromophobe RCC.
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Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Hepáticas , Femenino , Humanos , Persona de Mediana Edad , Fluorodesoxiglucosa F18 , Carcinoma de Células Renales/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagenRESUMEN
OBJECTIVE: To explore whether the markedly fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the liver (named hepatic superscan) is a specific manifestation of malignant involvement. METHODS: From January 2014 to June 2019, 23 patients with such presentations were retrospectively reviewed. 18F-FDG uptake was semiquantified using maximal standardized uptake value (SUVmax), liver to cerebellum (L/C) ratio, liver to mediastinum (L/M) ratio, mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Some related laboratory examinations were also collected and analyzed. For comparison, 37 patients with mildly and moderately uptake in the liver were selected as the control group. RESULTS: The hepatic SUVmax, L/C ratio, L/M ratio, SUVmean, MTV and TLG of the superscan group were significantly higher than that of mild- or moderate-uptake group (P < 0.005). Malignant hematological tumors accounted for 91.3% of the superscan group, which was significantly higher than 51.4% of mild- or moderate-uptake group (P = 0.004). ß2-microglobulin was observed to be significantly higher in the superscan group compared with mild- or moderate-uptake group (P < 0.001), but not lactate dehydrogenase (LDH) (P = 0.409). On the contrary, C-reactive protein (CRP) was significantly higher in mild- or moderate-uptake group than that in the superscan group (P < 0.001). CONCLUSION: Our study demonstrates that hepatic superscan is a strong indicator of malignant hematological tumors invading the liver.
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Neoplasias Hematológicas , Leucemia , Linfoma , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Humanos , Hígado/diagnóstico por imagen , Linfoma/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Estudios Retrospectivos , Carga TumoralRESUMEN
ABSTRACT: Intracranial diffuse embryonal tumor in the adult is rare. We report a young woman with a diffuse embryonal malignancy in the saddle area, which was depicted well by 11 C-choline PET/CT, superior to 18 F-FDG PET/CT and contrast-enhanced MRI. Under the guiding of 11 C-choline PET/CT, the biopsy was successfully performed and the diagnosis was established. This case highlights that 11 C-chione PET/CT may be useful to diagnose and delineate the intracranial diffuse embryonic tumors.
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Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Colina , Femenino , Fluorodesoxiglucosa F18 , Humanos , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: This study aimed to compare [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT with [18F]FDG PET/CT in the evaluation of initial gastric cancer. METHODS: We retrospectively compared [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT with [18F]FDG PET/CT in patients with initial gastric cancer from September 2020 to March 2021. Lesion detectability and the uptake of lesions quantified by the maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) were compared between the two modalities using the Wilcoxon signed-rank test, Mann-Whitney U test, and McNemar's chi-square test. RESULTS: A total of 61 patients (37 males, aged 23-81 years) were included, of which 22 underwent radical gastrectomy. For primary lesions, higher uptake of [68Ga]Ga-FAPI-04/[18F]FAPI-42 was observed compared to [18F]FDG (median SUVmax, 14.60 vs 4.35, p < 0.001), resulting in higher positive detection using [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT than [18F]FDG PET/CT (95.1% vs 73.8%, p < 0.001), particularly for tumors with signet-ring cell carcinoma (SRCC) (96.4% vs 57.1%, p < 0.001). [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT detected more positive lymph nodes than [18F]FDG PET/CT (637 vs 407). However, both modalities underestimated N staging compared to pathological N staging. [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT showed a higher sensitivity (92.3% vs 53.8%, p = 0.002) and peritoneal cancer index score (18 vs 3, p < 0.001) in peritoneum metastasis and other suspect metastases compared to [18F]FDG PET/CT. CONCLUSION: Our findings indicate that [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT outperformed [18F]FDG PET/CT in the evaluation of primary tumors with SRCC and peritoneum metastasis in initial gastric cancer. However, no clinically useful improvement was seen in N staging. KEY POINTS: ⢠The uptake of [68Ga]Ga-FAPI-04/[18F]FAPI-42 in primary tumor and metastasis was intensely higher than that of [18F]FDG (p < 0.001) in 61 patients with initial gastric cancer. ⢠[68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT had a higher sensitivity detection in primary tumors (95.1% vs 73.8%, p < 0.001) and peritoneal metastases (92.3% vs 53.8%, p = 0.002) than [18F]FDG PET/CT. ⢠[68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT depicted more positive lymph nodes than [18F]FDG PET/CT (637 vs 407); however, both underestimated N staging compared to pathological N staging.
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Neoplasias Peritoneales , Neoplasias Gástricas , Fluorodesoxiglucosa F18 , Radioisótopos de Galio , Humanos , Masculino , Neoplasias Peritoneales/diagnóstico por imagen , Peritoneo , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Quinolinas , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico por imagenRESUMEN
PURPOSE: To explore the expression of fibroblast activation protein (FAP) in lung cancer (LC) and its correlation with tumor glucose metabolism and histopathology. METHODS: From June 2018 to November 2020, 73 patients with newly diagnosed LC were included. Immunohistochemical staining was used to quantify FAP expression in tumors. The histopathological type and tumor grade were determined via histopathological examination. The tumor glucose metabolism parameters and tumor maximal diameter were measured via [18F] F-FDG PET/CT. Univariate and multivariate analysis were performed to study the correlation of FAP expression levels with glucose metabolism variables and tumor histopathology. RESULTS: Positive FAP expression was observed in 97.3% (71/73) LC lesions, which was significantly higher than 87.7% (64/73) of [18F] F-FDG positivity observed on PET/CT (χ2 = 4.818, P = 0.028). In 12 early adenocarcinomas (ADCs), only three lesions (25%) were positive for [18F] F-FDG on PET/CT; however, 10 lesions (83.3%) were positive for FAP. When FAP expression was classified into low level (scores ≤ 3) and high level (scores > 4), high FAP level was found in 80.8% tumors and low FAP level in the other 19.2% tumors. High FAP level was identified in 100.0% of squamous cell carcinomas (SCCs), 85.7% of ADCs, 66.7% (4/6) of large cell neuroendocrine carcinomas (LCNCs), and 40.0% (4/10) of small cell lung cancers (SCLCs) (P < 0.05). In non-mucinous ADC lesions, on univariate analysis, FAP expression level showed a close relationship with tumor metabolism parameters (maximal standard uptake value (SUVmax), mean standard uptake value (SUVmean), and total lesion glycolysis (TLG)), tumor diameter, tumor grade, and lesion attenuation (P < 0.05). CONCLUSION: The present study demonstrates that FAP is widely expressed in LC and shows great variation in different histopathological types. A high positive rate of FAP expression implies that FAP-targeted imaging may be a sensitive modality for diagnosing LC, especially in early ADCs. Further validation with such probes is warranted.
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Neoplasias Pulmonares , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fibroblastos/metabolismo , Fibroblastos/patología , Fluorodesoxiglucosa F18 , Glucosa , Humanos , Neoplasias Pulmonares/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios RetrospectivosRESUMEN
Background Gallium 68 (68Ga)-labeled fibroblast-activation protein inhibitor (FAPI) has recently been introduced as a promising tumor imaging agent. Purpose To compare 68Ga-FAPI PET/CT with fluorine 18 (18F)-labeled fluorodeoxyglucose (FDG) PET/CT in evaluating lung cancer. Materials and Methods In this prospective study conducted from September 2020 to February 2021, images from participants with lung cancer who underwent both 68Ga-FAPI and 18F-FDG PET/CT examinations were analyzed. The tracer uptakes, quantified by maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR), were compared for paired positive lesions between both modalities using the paired t test or Wilcoxon signed-rank test. Results Thirty-four participants (median age, 64 years [interquartile range: 46-80 years]; 20 men) were evaluated. From visual evaluation, 68Ga-FAPI PET/CT and 18F-FDG PET/CT showed similar performance in the delineation of primary tumors and detection of suspected metastases in the lungs, liver, and adrenal glands. The metabolic tumor volume in primary and recurrent lung tumors showed no difference between modalities (mean: 11.6 vs 10.8, respectively; P = .68). However, compared with 18F-FDG PET/CT, 68Ga-FAPI PET/CT depicted more suspected metastases in lymph nodes (356 vs 320), brain (23 vs 10), bone (109 vs 91), and pleura (66 vs 35). From semiquantitative evaluation, the SUVmax and TBR of primary or recurrent tumors, positive lymph nodes, bone lesions, and pleural lesions at 68Ga-FAPI PET/CT were all higher than those at 18F-FDG PET/CT (all P < .01). Although SUVmax of 68Ga-FAPI and 18F-FDG in brain metastases were not different (mean SUVmax: 9.0 vs 7.4, P = .32), TBR was higher with 68Ga-FAPI than with 18F-FDG (mean: 314.4 vs 1.0, P = .02). Conclusion Gallium 68-labeled fibroblast-activation protein inhibitor PET/CT may outperform fluorine 18-labeled fluorodeoxyglucose PET/CT in staging lung cancer, particularly in the detection of metastasis to the brain, lymph nodes, bone, and pleura. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Jacobson and Van den Abbeele in this issue.
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Neoplasias Pulmonares , Tomografía Computarizada por Tomografía de Emisión de Positrones , Femenino , Flúor , Fluorodesoxiglucosa F18 , Radioisótopos de Galio , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios ProspectivosRESUMEN
OBJECTIVES: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a fairly rare subtype of primary cutaneous lymphoma. This study aims to investigate the clinicopathologic features, 18F-FDG PET/CT findings, and outcome of patients with SPTCL. METHODS: A retrospective single-center study enrolled 11 patients with SPTCL between August 2010 and March 2020. A total of 26 18F-FDG PET/CT scans were performed, and the initial and follow-up PET/CT imaging features, clinicopathologic and immunohistochemical characteristics, and outcome were analyzed. RESULTS: The male-to-female ratio was 1.2. The mean age at diagnosis was 24.2 years (age range: 13-48 years). Histopathological examinations revealed atypical T-lymphocyte rimming of individual subcutaneous adipocytes, mostly with CD2+, CD3+, CD4-, CD5+, CD8+, CD56-, T-cell intracellular antigen-1+, Granzyme B+, and high Ki-67 index. Multiple large skin ulcerations with a maximum diameter of 10 cm were observed in one of the 11 patients (9.1%, 1/11), and hemophagocytic syndrome was found in another one. At initial PET/CT scans, the lesions in all 11 patients showed increased uptake of 18F-FDG with a wide range of maximum standard uptake value (SUVmax) from 2.0 to 14.9. The morphology of the lesions presented as multiple nodules and/or disseminated plaques mainly involving the trunk and/or limbs. Five patients had extracutaneous non-lymph node lesions with SUVmax of 5.6 ± 2.8 on 18F-FDG PET/CT. No significant correlation between SUVmax and Ki-67 index was observed (r = 0.19, P > 0.05). Follow-up 18F-FDG PET/CT scans in six patients showed complete remission of the disease in two, partial remission in three, and progressive disease in one. During the follow-up period, there was no death except for the patient with multiple ulcerations who died 4 months after diagnosis of SPTCL. CONCLUSIONS: SPTCL may be a group of heterogeneous diseases with varying degrees of 18F-FDG uptake. 18F-FDG PET/CT demonstrates its usefulness in detecting disease extent, providing diagnostic work-up, staging, and evaluating treatment response of SPTCL. Multiple large skin ulcerations may be a factor of poor prognosis for patients with SPTCL.
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OBJECTIVE: Lysosomal protein transmembrane 4 beta (LAPTM4B) is selectively expressed in hepatocellular carcinoma (HCC) cells and thus a potential biomarker for diagnosing HCC. In this study, we designed a novel 18F-labeled PET probe to non-invasively visualize LAPTM4B expression in mouse model of HCC tumor. METHODS: A PET targeting tracer named [18F]FP-LAP2H was radio-synthesized using a LAPTM4B targeting peptide, LAP2H, coupled with 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). Radio-stability, cell uptake, micro PET/CT imaging and ex vivo biodistribution were performed for determining its stability, cell binding specificity, and tumor targeting in vivo. RESULTS: [18F]FP-LAP2H was successfully synthesized with radiochemical yields of 6-14% (decay-corrected yield) and molar activity of 10-44 GBq/µmol. The tracer showed stable (~90%) in phosphate-buffered saline, pH 7.4, and in human serum (~80%) for 2 h. In vitro cell uptake studies indicated the radioactivity accumulation in HCC cells was LAPTM4B protein-specific. Micro PET/CT demonstrated that implanted LAPTM4B positive HepG2 and BEL7402 tumors could be clearly visualized. The ex vivo biodistribution studies demonstrated that the tumor/liver ratio were 1.80 ± 0.65 and 2.09 ± 0.68 in implanted HepG2 and BEL7402 tumors respectively. Negative control and blocking experiments revealed that the radioactivity uptake in the HCC tumor was LAPTM4B protein-specific. CONCLUSIONS: [18F]FP-LAP2H appears to be a potential PET tracer for imaging LAPTM4B-positive HCC tumor. Further endeavors need to do to improve tumor/liver ratio.
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Carcinoma HepatocelularRESUMEN
Facile automatic production is important for the application of prostate-specific membrane antigen (PSMA) tracers in clinical practice. We developed a new 18F-AlF-labelled PSMA probe-18F-AlF-PSMA-NF-and explore its automated production method and potential value in clinical settings. 18F-AlF-PSMA-NF was prepared using an automated method with dimethylformamide (DMF) as the solvent in a positron emission tomography (PET)-MF-2 V-IT-I synthesizer. Tracer characteristics were examined both in vitro and in vivo. Micro-PET/computed tomography (CT) was performed to investigate the utility of 18F-AlF-PSMA-NF for imaging PSMA-positive tumours in vivo. 18F-AlF-PSMA-NF was prepared automatically within 35 min with a non-attenuation correction yield of 37.9 ± 11.2%. The tracer was hydrophilic, had a high affinity for PSMA (Kd = 2.58 ± 0.81 nM), and showed stability in both in vitro and in vivo conditions. In the cellular experiments, 18F-AlF-PSMA-NF uptake in PSMA-positive LNCaP cells was significantly higher than that in PSMA-negative PC-3 cells (P < 0.001), and could be blocked by excess ZJ-43-a PSMA inhibitor (P < 0.001). LNCaP tumours were clearly visualized by 18F-AlF-PSMA-NF on micro-PET/CT, with a high level of uptake (13.72 ± 2.01 percent injected dose per gram of tissue [%ID/g]) and high tumour/muscle ratio (close to 50:1). The PSMA-positive LNCaP tumours had a significantly higher uptake than PSMA-negative PC-3 tumours (13.72 ± 2.01%ID/g vs. 1.07 ± 0.48%ID/g, t = 10.382, P < 0.001), and could be blocked by ZJ-43 (13.72 ± 2.01%ID/g vs. 2.77 ± 1.44%ID/g, t = 8.14, P < 0.001). A new 18F-AlF-labelled PSMA probe-18F-AlF-PSMA-NF-was successfully developed and can be prepared automatically. It has the biological characteristics resembling that of a PSMA-based probe and can potentially be used in clinical settings.
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Antígenos de Superficie , Radioisótopos de Flúor , Glutamato Carboxipeptidasa II , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Radiofármacos , Animales , Antígenos de Superficie/química , Antígenos de Superficie/farmacología , Radioisótopos de Flúor/química , Radioisótopos de Flúor/farmacología , Glutamato Carboxipeptidasa II/síntesis química , Glutamato Carboxipeptidasa II/química , Glutamato Carboxipeptidasa II/farmacocinética , Glutamato Carboxipeptidasa II/farmacología , Humanos , Marcaje Isotópico , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células PC-3 , Neoplasias de la Próstata/metabolismo , Radiofármacos/síntesis química , Radiofármacos/química , Radiofármacos/farmacocinética , Radiofármacos/farmacología , Distribución TisularRESUMEN
PURPOSE: Accurate prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is crucial. We developed an objective and robust deep learning-based fully-automated tool called the DeepPET-OPSCC biomarker for predicting overall survival (OS) in OPSCC using [18F]fluorodeoxyglucose (FDG)-PET imaging. EXPERIMENTAL DESIGN: The DeepPET-OPSCC prediction model was built and tested internally on a discovery cohort (n = 268) by integrating five convolutional neural network models for volumetric segmentation and ten models for OS prognostication. Two external test cohorts were enrolled-the first based on the Cancer Imaging Archive (TCIA) database (n = 353) and the second being a clinical deployment cohort (n = 31)-to assess the DeepPET-OPSCC performance and goodness of fit. RESULTS: After adjustment for potential confounders, DeepPET-OPSCC was found to be an independent predictor of OS in both discovery and TCIA test cohorts [HR = 2.07; 95% confidence interval (CI), 1.31-3.28 and HR = 2.39; 95% CI, 1.38-4.16; both P = 0.002]. The tool also revealed good predictive performance, with a c-index of 0.707 (95% CI, 0.658-0.757) in the discovery cohort, 0.689 (95% CI, 0.621-0.757) in the TCIA test cohort, and 0.787 (95% CI, 0.675-0.899) in the clinical deployment test cohort; the average time taken was 2 minutes for calculation per exam. The integrated nomogram of DeepPET-OPSCC and clinical risk factors significantly outperformed the clinical model [AUC at 5 years: 0.801 (95% CI, 0.727-0.874) vs. 0.749 (95% CI, 0.649-0.842); P = 0.031] in the TCIA test cohort. CONCLUSIONS: DeepPET-OPSCC achieved an accurate OS prediction in patients with OPSCC and enabled an objective, unbiased, and rapid assessment for OPSCC prognostication.