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Predictive value of ¹⁸F-FDG PET conventional parameters and radiomics features for invasive breast cancer patients with uncertain HER2 expression by immunohistochemistry

Yufan ZHANG ; Jianjing LIU ; Xiaofeng LI ; Wengui XU

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):641-646. doi:10.3760/cma.j.issn.2095-2848.2019.11.001

Objective: To explore the predictive value of ¹⁸F-fluorodeoxyglucose (FDG) PET conventional parameters and radiomics features for human epidermal growth factor receptor 2 (HER2) expression which was uncertain by immunohistochemistry (IHC) detection in invasive breast cancer. Methods: From April 2012 to December 2017, 76 patients (all were females, age: (50.8±10.9) years) with invasive breast cancer and with uncertain HER2 expression by IHC in Tianjin Medical University Cancer Institute and Hospital were enrolled retrospectively. The ¹⁸F-FDG PET/CT images before treatment were reviewed and the expression of HER2 were confirmed by fluorescence in situ hybridization (FISH). The tumor lesions were manually outlined, and the radiomics features from PET images were extracted. Wilcoxon test was used to determine whether there was difference in PET conventional metabolic parameters (maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and radiomics features between HER2-negative and HER2-positive groups. The receiver operating characteristic (ROC) curve analysis was used to compare the predictive efficacy of PET radiomics features for HER2 expression. Results: There were 41 HER2-positive patients and 35 HER2-negative patients. No significant differences in PET conventional metabolic parameters between different HER2 expression groups were observed (U values: from -1.598 to 1.551, all P>0.05). A total of 38 PET radiomics features were extracted, and there were significant differences in gray mean, correlation, contrast, inertia, and inverse different moments between 2 groups(U values: from -2.413 to 2.527, all P<0.05). The area under the curve of the above 5 parameters for prediction of HER2 expression were 0.643, 0.638, 0.647, 0.644 and 0.643, respectively, and the contrast was the best parameter. Conclusions PET radiomics features can effectively identify HER2 expression in patients with invasive breast cancer to some extent, and the contrast may be the best. Conventional metabolic parameters have limited predictive value.

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Diagnostic value of ¹¹C-methionine PET/CT imaging for detecting the recurrence of supratentorial glioma

Zhen QIAO ; Xiaobin ZHAO ; Qian CHEN ; Kai WANG ; Di FAN ; Lin AI

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):647-652. doi:10.3760/cma.j.issn.2095-2848.2019.11.002

Objective: To assess the diagnostic values of ¹¹C-methionine (MET) PET/CT semiquantitative parameters for detecting recurrence in patients who were diagnosed with suspicious recurrence by MRI after resection of supratentorial gliomas. Methods: A total of 164 patients (107 males, 57 females, age 6-74 years; high-grade 94, low-grade 63, unclear 7) with supratentorial gliomas who underwent ¹¹C-MET PET/CT between June 2015 and June 2017 in Beijing Tiantan Hospital were enrolled respectively. All patients were with suspicious recurrence after surgery showed by MRI and followed up for 6 months at least. The final diagnosis was determined with histopathological analysis or clinical follow-up. The maximum and mean standardized uptake value (SUV_max and SUV_mean), tumor-to-background ratios (TBR) of SUV_max and SUV_mean (TBR_max and TBR_mean) were recorded and compared between patients with recurrence or without recurrence using independent-sample t test. Receiver operating characteristic (ROC) curves were drawn to determine the threshold, and the diagnostic sensitivity and specificity of each parameter were calculated. Results: According to the clinical diagnosis, there were 139 patients with recurrence and 25 without recurrence. SUV_max, SUV_mean, TBR_max and TBR_mean were significantly higher for patients with recurrence than those without recurrence (4.19±1.95 vs 2.59±1.18, 2.34±1.08 vs 1.46±0.72, 2.95±1.17 vs 1.83±0.79, 2.64±1.11 vs 1.59±0.71; t values: 5.126-6.183, all P<0.01), but there was no difference in the areas under the ROC curve (AUC) for diagnosis of recurrence with the 4 parameters (z values: 0.265-1.674, all P>0.05), for which the optimal cut-off values were 3.05, 1.65, 1.96 and 1.79, respectively, and the corresponding sensitivities/specificities for the diagnosis of recurrence were 67.6%(94/139)/100%(25/25), 67.6%(94/139)/100%(25/25), 79.9%(111/139)/100%(25/25), 74.8%(104/139)/100%(25/25), respectively. Patients with (n=81) or without (n=13) recurrence had different semiquantitative parameters in high-grade glioma group (t values: 5.137-5.871, all P<0.01), and the AUC for TBR_mean was greater than that for SUV_mean (0.858 vs 0.802; z=1.982, P<0.05). Patients with (n=54) or without (n=9) recurrence in low-grade glioma group showed significant difference in the 4 parameters (t values: 2.730-7.009, all P<0.01), while the AUCs of the 4 parameters were not significantly different (z values: 0.444-1.407, all P>0.05). Among 37 patients with recurrence confirmed by pathology, there were no significant differences in the semiquantitative parameters between the high-grade and low-grade glioma groups and AUCs were not different either (t values: 1.387-1.937, z values: 0.106-1.752, all P>0.05). Conclusions Semiquantitative parameters of ¹¹C-MET PET/CT are equally accurate in the differentiation of recurrence from radiation injury in patients with gliomas, while TBR_mean was superior than SUV_mean in patients with the high-grade gliomas. Among the patients with recurrence confirmed by pathology, the value of the semiquantitative parameter is limited for the identification of high- and low- grade gliomas.

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¹⁸F-FDG PET/CT imaging manifestations of peritoneal carcinomatosis from colorectal cancer and its clinical significance

Chunfeng SUN ; Zhonghua TAN ; Yan GAO ; Jianwei ZHU ; Xiaoying MAO ; Chengchun GE ; Shanlei BAO

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):653-656. doi:10.3760/cma.j.issn.2095-2848.2019.11.003

Objective: To analyze ¹⁸F-fluorodeoxyglucose(FDG) PET/CT imaging manifestations in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) and investigate its clinical significance. Methods: From May 2016 to August 2018, 46 patients (25 males, 21 females; age range: 36-82(62.0±10.4) years) with PC from CRC who underwent ¹⁸F-FDG PET/CT imaging in Affiliated Hospital of Nantong University and had complete clinical data were retrospectively analyzed. The peritoneal carcinomatosis index (PCI) grading system was used to evaluate the PC lesions. Independent-sample t test and Kruskal-Wallis H test were used for data analysis. Results: There were various CT manifestations of PC, while FDG metabolism on PET was observed in all 46 patients. Patients were divided into different groups according to the location of the primary CRC lesion. The diameter of PC lesion in the left colon group was (2.46±1.26) cm, which was significantly different from that of the rectum group ((3.19±1.72) cm; t=-2.77, P<0.01). The maximum standardized uptake value (SUV_max) in the right colon group were significantly higher than that in the left colon group (9.16±4.79 vs 6.99±3.50; t=2.92, P<0.01). The PCI score ranged from 1 to 30 in 46 patients, and there was no significant difference in PCI score distribution (≥20 vs <20) among the right colon group, left colon group and rectum group (H=0.242, P>0.05). Ten patients had abdominal and pelvic effusion. Conclusion ¹⁸F-FDG PET/CT can well display the PC in patients with CRC, and the combination of PCI and ¹⁸F-FDG PET/CT plays an important role in the diagnosis and treatment of PC.

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Relationship between BRAF^V600E mutation and metastasis after thyroidectomy in papillary thyroid carcinoma with different recurrence risk stratification

Zhen JIA ; Ruihong YAN ; Changming ZHANG ; Hongyan ZHAI ; Tianzheng YANG ; Zhenhu ZHOU

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):657-660. doi:10.3760/cma.j.issn.2095-2848.2019.11.004

Objective: To investigate the relationship between V-raf murine sarcoma viral oncogene homologue B1 (BRAF)^V600E mutation and metastasis after thyroidectomy in papillary thyroid carcinoma (PTC) with different recurrence risk stratification. Methods: From March 2014 to September 2017, 134 PTC patients (45 males, 89 females; age: 16-72 years) who underwent ¹³¹I treatment in the Department of Nuclear Medicine of Liaocheng People′s Hospital and had undergone BRAF^V600E mutation detection were retrospectively analyzed. The recurrence risk during surgery was divided into 3 levels: low-, medium- and high-risk. Each recurrence risk group was divided into 3 subgroups according to the postoperative follow-up results: non-metastasis group, cervical lymph node metastasis group and pulmonary metastasis group. BRAF^V600E mutation rates in different groups were compared (χ² test). Results: The BRAF^V600E mutation rate was 55.22%(74/134) in 134 PTC patients. The mutation rates were not significantly different in the 3 metastasis subgroups for low-risk patients (n=46; χ²=2.39, P>0.05). In medium-risk patients (n=47), the mutation rate in neck lymph node metastasis group (16/19) was higher than that in pulmonary metastasis group (3/8) and non-metastasis group (25.00%, 5/20; χ² values: 5.89 and 13.75, both P<0.05), while there was no difference between pulmonary metastasis group and non-metastasis group (χ²=0.44, P>0.05). In high risk patients (n=41), the mutation rate in neck lymph node metastasis group (85.00%, 17/20) was higher than that in the pulmonary metastasis group (5/13) and non-metastasis group (1/8; χ² values: 7.68 and 13.08, both P<0.01), while there was no difference between pulmonary metastasis group and non-metastasis group (χ²=1.64, P>0.05). Conclusion The BRAF^V600E mutation is closely related to neck lymph node metastasis after operation in middle- and high-risk patients with PTC, but it does not significantly increase the probabilities of neck lymph node metastasis in low-risk patients and pulmonary metastasis in low-, medium- and high-risk patients.

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Predictive value of stimulated thyroglobulin before the first ¹³¹I ablation for metastasis of differentiated thyroid carcinoma in children and adolescents

Xianmin DING ; Ying DING ; Sen WANG ; Guang YANG ; Fuqiang ZHANG ; Deyu LI ; Qiang LI ; Wenliang LI ; Hui YANG

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):661-664. doi:10.3760/cma.j.issn.2095-2848.2019.11.005

Objective: To investigate the clinical value of pre-ablation stimulated thyroglobulin (psTg) in the prediction of metastasis of differentiated thyroid carcinoma (DTC) in children and adolescents. Methods: The study included 51 children and adolescent patients (20 males, 31 females, age: 8-18(13.5±3.0) years) with DTC who had undergone total thyroidectomy and lymphadenectomy and were going to have the first ¹³¹I ablation therapy from March 2012 to December 2017 in the Affiliated Cancer Hospital of Zhengzhou University. Patients′ serum thyroglobulin antibody (TgAb) levels were normal. They were divided into M0 group (without metastasis) and M1 group (with metastasis). The psTg difference between the two groups was compared using Mann-Whitney U test. The receiver operating characteristic (ROC) curves and diagnostic critical point (DCP) of psTg for the metastasis prediction were analyzed. Results: The psTg levels of M0 group (n=20) and M1 group (n=31) were 5.76(3.38, 18.51) μg/L and 280.46(37.66, 470.00) μg/L, respectively, and the difference between the two groups was statistically significant (U=41, P<0.05). The area under the ROC curve of psTg was 0.934 (95% CI: 0.869-0.999) with the sensitivity, specificity and accuracy of 80.6%(25/31), 100%(20/20) and 88.2%(45/51) respectively, with the DCP value of 31.98 μg/L. Conclusion The psTg value detected before the first ¹³¹I treatment has an important predictive value for postoperative metastasis of DTC in children and adolescents.

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¹⁷⁷Lu-PSMA-I&T automated radiolabeling and preclinical prostate cancer targeting research

Lulu ZHANG ; Fan QIU ; Pengjun ZHANG ; Zhihong XU ; Ting BU ; Shiming ZANG ; Shuyue AI ; Feng WANG

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):665-669. doi:10.3760/cma.j.issn.2095-2848.2019.11.006

Objective: To synthesis ¹⁷⁷Lu-prostate specific membrane antigen (PSMA)-I&T with automated module, evaluate the biodistribution and pharmacokinetics in mice and study the targeting property in human prostate cancer cell line LNCaP Clone FGC. Methods: The iQS-TS automated module was applied in labeling ¹⁷⁷Lu-PSMA-I&T. Radiochemical purity and stability were determined with high performance liquid chromatography (HPLC). The biodistribution was observed in normal ICR mice and U-SPECT/CT imaging was performed in LNCaP Clone FGC tumor-bearing mice. Independent-sample t test was used to analyze the data. Results: ¹⁷⁷Lu-PSMA-I&T was stable in vitro and in vivo, with the radiolabeled yield of (91.5±4.9)% and radiochemical purity >99%. The half maximal inhibitory concentration (IC₅₀) of ¹⁷⁷Lu-PSMA-I&T binding to LNCaP Clone FGC cells was (26.74±3.53) nmol/L. The uptake of ¹⁷⁷Lu-PSMA-I&T by LNCaP Clone FGC cells increased with time and significantly decreased after the inhibitor addition (t values: 4.301-27.483, all P<0.05). ¹⁷⁷Lu-PSMA-I&T was cleared from blood rapidly and predominantly excreted by kidneys. Significant radioactive uptake was observed in tumors with a long retention time. Conclusion ¹⁷⁷Lu-PSMA-I&T can be produced in a convenient and efficient procedure using iQS-TS automated module, with good biological properties and excellent affinity and targeting property towards prostate cancer cells, which making it a potential radiopharmaceutical for prostate cancer therapy.

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Expression and clinical significance of SLC5A5 gene of sodium/iodide symporter in thyroid carcinoma based on the biological information database

Junyu TONG ; Tingting QIAO ; Zhongwei LYU ; Dan LI

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):670-674. doi:10.3760/cma.j.issn.2095-2848.2019.11.007

Objective: To analyze the expression and clinical significance of solute carrier family 5 member 5 (SLC5A5), the coding gene of sodium/iodide symporter (NIS), in thyroid carcinoma. Methods: The messenger RNA (mRNA) expression of SLC5A5 in thyroid carcinoma and normal thyroid tissues from The Cancer Genome Atlas (TCGA) was compared using independent-sample t test and results were shown in one scatter plot. The relation between clinical features of thyroid carcinoma and the changes of SLC5A5 mRNA was analyzed on LinkedOmics using Kruskal-Wallis test or Wilcoxon test. Results: Data from TCGA showed that the SLC5A5 mRNA expression in thyroid carcinoma (1.419±0.049) was significantly reduced compared with that in normal thyroid tissues (3.301±0.087; t=12.66, P<0.01). The expression of SLC5A5 mRNA in thyroid carcinoma is affected by ethnicity (χ²=0.300, P<0.05). Moreover, the expression of SLC5A5 mRNA were decreased with the increase of pathologic grading (Ⅰ, Ⅱ, Ⅲ, Ⅳ) and T, N, M stages (χ² values: 0.114, 0.215, z values: -0.345, -0.102, all P<0.05). Conclusions The expression level of SLC5A5 mRNA is associated with clinical characteristic of thyroid carcinoma. SLC5A5 mRNA has the potential to become one candidate biomarker to assess disease and predict the development of thyroid carcinoma.

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Research progress of brown adipose tissue imaging technology

Xiaonan SHAO ; Xiaoliang SHAO ; Zhenxing JIANG ; Yuetao WANG

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):685-687. doi:10.3760/cma.j.issn.2095-2848.2019.11.012

Diabetes, obesity, and metabolic diseases are globally prevalent, and induction and increase of endogenous energy consumption, especially activation of brown adipose tissue (BAT), is a new therapeutic target. Non-invasive imaging techniques, including radionuclide imaging, MRI, ultrasound imaging, and optical imaging, have attracted wide attention in BAT monitoring and have good application prospects. This article reviews the progress and application of these imaging techniques in BAT monitoring.

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Research progress of CD13-targeted molecular probe in tumor neovascularization imaging and therapy

Minghao WU ; Yanyan ZHANG ; Lin CAO ; Xuening ZHANG ; Zhaoxiang YE

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):688-693. doi:10.3760/cma.j.issn.2095-2848.2019.11.013

Tumor neovascularization plays an important role in the occurrence, development and metastasis of cancer. Non-invasive quantification and detection of tumor neovascularization is crucial for early diagnosis and prognosis assessment of cancer. Targeted molecular imaging has arisen in vascular targeting imaging and precise treatment based on the molecular characteristics of neovascularization. Aminopeptidase N (APN, or CD13) is a multifunctional membrane-bound exopeptidase that is overexpressed in neovascular endothelial cells and some tumor cells but rarely expressed in normal blood vessels, which makes it a potential target for tumor neovascularization imaging and anti-angiogenic therapy. This review summarizes the application progress and the future development trend of target molecular imaging and precise treatment based on CD13.

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Environment-responsive fluorescence probes in image-guided surgery

Jing ZHU ; Chengchao CHU ; Gang LIU

Chinese Journal of Nuclear Medicine and Molecular Imaging.2019;39(11):694-697. doi:10.3760/cma.j.issn.2095-2848.2019.11.014

Unlike conventional imaging technologies, fluorescent imaging benefits from its safety, high-spatial resolution and real-time capability, which make it a highly adoptable imaging method for tumor detection and image-guided surgery in clinics. There are two types of fluorescent probes, including always-on type and environment-responsive type, wherein environment-responsive probes are preferred due to higher target-to-background ratios, which can improve sensitivity and specificity. The environment-responsive probes include enzyme-reactive probes, pH-sensitive probes and hypoxia responsive probes. This review summarizes recent progress in environment-responsive probes, and discusses their potentials in tumor detection and image-guided surgery.

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