First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer

BackgroundDeath receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers.MethodsBalb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo. In the clinical study, patients with GI cancers planning to undergo surgical operation were enrolled and underwent 18F-FDG and 89Zr-CTB006 PET/CT. The tumor tissues were obtained through surgical operation and DR5 expression levels were confirmed by RNAscope.ResultsPreclinical studies showed that 89Zr-CTB006 PET could specifically detect DR5 expression levels in vivo. Twenty-one patients, including nine gastric cancers and 12 colorectal cancers, were enrolled. The biodistribution showed high uptake in the liver and spleen and low uptake in the brain, lung and muscle with an acceptable whole-body dosimetry of 0.349 mSv/MBq. Strikingly, the adrenal glands maintained stable high uptake over the entire examination in all patients. The tumor lesions showed different levels of uptake of 89Zr-CTB006 with a mean maximum standardized uptake value (SUVmax) of 6.63±3.29 (range 1.8–13.8). Tumor tissue was obtained from 18 patients, and 89Zr-CTB006 uptake in patients with RNAscope scores of 3–4 was significantly higher than that in patients with scores of 0–2. An SUVmax of 9.3 at 48 hours and 6.3 at 72 hours could be used to discriminate the DR5 expression status of tumors both with a sensitivity and specificity of 100% and 92.9%, respectively.Conclusions89Zr-CTB006 PET/CT is capable of detecting DR5 expression in cancer patients and is a promising approach to screen patients with DR5 overexpression.

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A Prospective Comparison of [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT in Patients With Various Cancers

10.21203/rs.3.rs-873563/v1 ◽

2021 ◽

Author(s):

Kongzhen Hu ◽

Lijuan Wang ◽

Hubing Wu ◽

Shun Huang ◽

Ying Tian ◽

...

Keyword(s):

Standardized Uptake Value ◽

Tumor Detection ◽

Whole Body ◽

Acquisition Time ◽

Bone Lesions ◽

Tumor Uptake ◽

Detection Ability ◽

Pet Ct ◽

High Level

Abstract Purpose: [18F]FAPI-42 is a new fibroblast activation protein (FAP) specific tracer used for cancer imaging. Here, we describe the in vivo evaluation of [18F]FAPI-42 and compared intra-individual biodistribution, tumor uptake, and detection ability to [68Ga]Ga-FAPI-04.Methods: A total of 22 patients with various types of cancer received [18F]FAPI-42 whole-body positron emission tomography/computed tomography (PET/CT). Among them, 4 patients underwent PET/CT scans, including an early dynamic 20-min, static 1-hour and static 2-hours. The in vivo biodistribution in normal organs and tumor uptake were semi-quantitatively evaluated using the standardized uptake value (SUV) and tumor-to-background ratio (TBR). Furthermore, both [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT were performed in 12 patients to compare biodistribution, tumor uptake, and tumor detection ability.Results: [18F]FAPI-42 uptake in the tumors was rapid and reached a high level with an average SUVmax of 15.8 at 18 minutes, which stayed at a similarly high level to 2 hours. The optimal image acquisition time for [18F]FAPI-42 was determined to be 1 hour post injection. Compared to [68Ga]Ga-FAPI-04, [18F]FAPI-42 had a higher uptake in the parotid, salivary gland, thyroid, and pancreas (P < 0.05). For tumor detection, [18F]FAPI-42 had a high uptake and could be clearly visualized in the lesions. [18F]FAPI-42 and [68Ga]Ga-FAPI-04 showed the same detectability for 144 positive lesions. In addition, [18F]FAPI-42 had a higher SUVmax in liver and bone lesions (P < 0.05) and higher TBRs in liver, bone, lymph node, pleura and peritonea lesions (all P < 0.05).Conclusion: The present study demonstrates that [18F]FAPI-42 is a good tracer for imaging malignant tumors and exhibited comparable lesion detectability to [68Ga]Ga-FAPI-04. The 1-hour scan is an appropriate time for tumor detection and is superior to the early 10-min scan for the detection of small lesions.Trial registration Chinese Clinical Trial Registry (ChiCTR2100045757)

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Oncogenic long intervening noncoding RNA Linc00284 promotes c-Met expression by sponging miR-27a in colorectal cancer

Oncogene ◽

10.1038/s41388-021-01839-w ◽

2021 ◽

Author(s):

Jun You ◽

Jiayi Li ◽

Chunlin Ke ◽

Yanru Xiao ◽

Chuanhui Lu ◽

...

Keyword(s):

Colorectal Cancer ◽

Noncoding Rna ◽

Cell Function ◽

In Vivo Studies ◽

Tumor Xenograft ◽

Luciferase Reporter ◽

Expression Levels ◽

Clinical Biomarkers ◽

Tumor Tissues

AbstractEmerging evidences suggest that long noncoding RNA (lncRNA) plays a vital role in tumorigenesis and cancer progression. Here, the aim of this study is to investigate the biological function of long intervening noncoding RNA Linc00284 in colorectal cancer (CRC). The expression levels of Linc00284, miR-27a and c-Met were evaluated by qPCR and/or Western blotting. Immunohistochemistry was used to detect the expression of Ki67 and Phh3 in tumor tissues. The interaction between Linc00284, miR-27a and c-Met was validated by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell function experiments, including CCK-8, wound-healing and transwell invasion assays, were conducted. The in vivo studies were performed with the subcutaneous tumor xenograft mouse models. Our findings reveal that Linc00284 is upregulated in CRC tissues and colorectal cancer cell lines HCT116 and SW480 in comparison with corresponding para-carcinoma tissues and human fetal colonic mucosa cells FHC. High expression of Linc00284 in tumor tissues is associated with tumor metastasis and predicts a poor clinical outcome in CRC patients. Serum Linc00284 is increased, while miR-27a is decreased in CRC patients compared to healthy controls. ROC curve analysis indicates that serum Linc00284 and miR-27a produce the area under the curve (AUC) value of at 0.8151 and 0.7316 in patients with colorectal cancer compared to healthy individuals, respectively. Additionally, results in vitro and in vivo experiments suggest that Linc00284 silencing significantly suppresses CRC cell proliferation and/or invasion. Mechanistically, Linc00284 promotes c-Met expression by acting as miR-27a sponge, leading to the activation of downstream signaling pathways, thereby causing malignant phenotypes of CRC cells. Taken together, Linc00284 exhibits oncogenic function and the disturbance of Linc00284/miR-27a/c-Met regulatory axis contributes to CRC progression, providing new insight into the pathogenesis of colorectal cancer. Importantly, the expression levels of serum Linc00284 and miR-27a may serve as clinical biomarkers for CRC diagnosis.

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SUVmax of FDG PET-CT Can Be Used As An Identifier of Lesion for AI To Interpret Radiology Reports

10.21203/rs.3.rs-61799/v1 ◽

2020 ◽

Author(s):

Kenji Hirata ◽

Osamu Manabe ◽

Keiichi Magota ◽

Sho Furuya ◽

Tohru Shiga ◽

...

Keyword(s):

Fdg Pet ◽

Standardized Uptake Value ◽

Local Maximum ◽

Ct Images ◽

Whole Body ◽

Training Dataset ◽

Imaging Biomarkers ◽

Radiology Reports ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Background Radiology reports contribute not only to the particular patient, but also to constructing massive training dataset in the era of artificial intelligence (AI). The maximum standardized uptake value (SUVmax) is often described in daily radiology reports of FDG PET-CT. If SUVmax can be used as an identifier of lesion, that would greatly help AI interpret radiology reports. We aimed to clarify whether the lesion can be localized using SUVmax written in radiology reports.Methods The institutional review board approved this retrospective study. We investigated a total of 112 lesions from 30 FDG PET-CT images acquired with 3 different scanners. SUVmax was calculated from DICOM files based on the latest Quantitative Imaging Biomarkers Alliance (QIBA) publication. The voxels showing the given SUVmax were exhaustively searched in the whole-body images and counted. SUVmax was provided with 5 different degrees of precision: integer (e.g., 3), 1st decimal places (DP) (3.1), 2nd DP (3.14), 3rd DP (3.142), and 4th DP (3.1416). For instance, when SUVmax=3.14 was given, the voxels with 3.135≤SUVmax<3.145 were extracted. We also evaluated whether local maximum restriction could improve the identifying performance, where only the voxels showing the highest intensity within some neighborhood were considered. We defined that “identical detection” was achieved when only single voxel satisfied the criterion.Results A total of 112 lesions from 30 FDG PET-CT images were investigated. SUVmax ranged from 1.3 to 49.1 (median = 5.6, IQR = 5.2). Generally, when larger and more precise SUVmax values were given, fewer voxels satisfied the criterion. The local maximum restriction was very effective. When SUVmax was determined to 4 decimal places (e.g., 3.1416) and the local maximum restriction was applied, identical detection was achieved in 33.3% (lesions with SUVmax<2), 79.5% (2≤SUVmax<5), and 97.8% (5≤SUVmax) of lesions.Conclusions SUVmax of FDG PET-CT can be used as an identifier to localize the lesion if precise SUVmax is provided and local maximum restriction was applied, although the lesions showing SUVmax<2 were difficult to identify. The proposed method may have potential to make use of radiology reports retrospectively for constructing training datasets for AI.

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Assessment of biological parameters in head and neck cancer based on in vivo distribution of 18F-FDG-FLT-FMISO-PET/CT images

Tumori Journal ◽

10.1177/0300891619868012 ◽

2019 ◽

Vol 106 (1) ◽

pp. 33-38

Author(s):

Paulina Cegla ◽

Joanna Kazmierska ◽

Sebastian Gwozdz ◽

Rafal Czepczynski ◽

Julian Malicki ◽

...

Keyword(s):

Head And Neck ◽

Primary Tumor ◽

Tumor Biology ◽

Standardized Uptake Value ◽

Intratumor Heterogeneity ◽

Biological Parameters ◽

Newly Diagnosed ◽

In Vivo Distribution ◽

Pet Ct

Objective: Several genetic analyses have identified tumor diversity not only among tumors from different patients (intertumor heterogeneity) but also within individual tumors (intratumor heterogeneity). The aim of this study was to analyze the intratumor heterogeneity and other biological parameters based on in vivo distribution in triple-tracer positron emission tomography with computed tomography (PET/CT) study in patients with newly diagnosed head and neck (H&N) cancer. Methods: Thirty-six patients with newly diagnosed H&N cancer were included in the study. Institutional Bioethical Committee approved the study protocol and informed consent was received from every participant. All patients underwent series of 3 PET/CT scans with [18F]Fluorodeoxyglucose (18F-FDG-PET), [18F]Fluorothymidine (18F-FLT-PET), and [18F]Fluoromisonidazole (18F-FMISO-PET) before treatment. Scans were performed on separate days, within a timeframe of 2 weeks. Several PET/CT parameters grading tumor biology including maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), its equivalent (total hypoxic lesion [TLH] and total proliferative lesion [TLP]), and heterogeneity (area under the curve–cumulative SUV histogram) for the primary tumor were compared. Results: All patients showed increased uptake of 18F-FDG in primary tumor, ranging from 2.29 to 14.89 SUVmax. Respectively, SUVmax values for 18F-FLT ranged from 0.93 to 16.11 and for 18F-FMISO 0.36–4.07. Based on 3-year follow-up, we divided patients in terms of survival forecasts (first with good prognosis and second with worse). Higher values of TLG/TLP/TLH and SUVmax were observed in the second group in all 3 tracers (for 18F-FDG: 167.40 vs 100.32, 11.15 vs 8.95; for 18F-FLT: 116.61 vs 60.67, 7.09 vs 5.47; for 18F-FMISO: 37.34 vs 22.30, 1.70 vs 1.61 respectively). Statistically significant differences were shown in SUVmax in 18F-FDG and 18F-FLT ( P<0.034, P<0.034, respectively; in TLG, P=0.05; TLP, P=0.04; and TLH, P=0.05). Conclusion: Our preliminary results suggest worse prognosis in patients with higher heterogeneity values of primary tumor in proliferation and hypoxia images and combination of metabolic and volumetric parameters in TLG and its equivalent and heterogeneity of primary tumor seems to be a prognostic factor.

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A Preliminary Study to Use SUVmax of FDG PET-CT as an Identifier of Lesion for Artificial Intelligence

Frontiers in Medicine ◽

10.3389/fmed.2021.647562 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kenji Hirata ◽

Osamu Manabe ◽

Keiichi Magota ◽

Sho Furuya ◽

Tohru Shiga ◽

...

Keyword(s):

Artificial Intelligence ◽

Fdg Pet ◽

Standardized Uptake Value ◽

Local Maximum ◽

Ct Images ◽

Whole Body ◽

Imaging Biomarkers ◽

Pet Ct ◽

Preliminary Study ◽

Fdg Pet Ct

Background: Diagnostic reports contribute not only to the particular patient, but also to constructing massive training dataset in the era of artificial intelligence (AI). The maximum standardized uptake value (SUVmax) is often described in daily diagnostic reports of [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) – computed tomography (CT). If SUVmax can be used as an identifier of lesion, that would greatly help AI interpret diagnostic reports. We aimed to clarify whether the lesion can be localized using SUVmax strings.Methods: The institutional review board approved this retrospective study. We investigated a total of 112 lesions from 30 FDG PET-CT images acquired with 3 different scanners. SUVmax was calculated from DICOM files based on the latest Quantitative Imaging Biomarkers Alliance (QIBA) publication. The voxels showing the given SUVmax were exhaustively searched in the whole-body images and counted. SUVmax was provided with 5 different degrees of precision: integer (e.g., 3), 1st decimal places (DP) (3.1), 2nd DP (3.14), 3rd DP (3.142), and 4th DP (3.1416). For instance, when SUVmax = 3.14 was given, the voxels with 3.135 ≤ SUVmax < 3.145 were extracted. We also evaluated whether local maximum restriction could improve the identifying performance, where only the voxels showing the highest intensity within some neighborhood were considered. We defined that “identical detection” was achieved when only single voxel satisfied the criterion.Results: A total of 112 lesions from 30 FDG PET-CT images were investigated. SUVmax ranged from 1.3 to 49.1 (median = 5.6). Generally, when larger and more precise SUVmax values were given, fewer voxels satisfied the criterion. The local maximum restriction was very effective. When SUVmax was determined to 4 decimal places (e.g., 3.1416) and the local maximum restriction was applied, identical detection was achieved in 33.3% (lesions with SUVmax < 2), 79.5% (2 ≤ SUVmax < 5), and 97.8% (5 ≤ SUVmax) of lesions.Conclusion: In this preliminary study, SUVmax of FDG PET-CT could be used as an identifier to localize the lesion if precise SUVmax is provided and local maximum restriction was applied, although the lesions showing SUVmax < 2 were difficult to identify. The proposed method may have potential to make use of diagnostic reports retrospectively for constructing training datasets for AI.

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Prognostic Value of Metabolic Parameters Measured By 18F-FDG PET/CT In Patients With Metastatic Cutaneous Malignant Melanoma

10.21203/rs.3.rs-152697/v1 ◽

2021 ◽

Author(s):

Ruihe Lai ◽

Chong Jiang ◽

Zhaoqun Chu ◽

Zhengyang Zhou ◽

Yue Teng ◽

...

Keyword(s):

Malignant Melanoma ◽

Fdg Pet ◽

Standardized Uptake Value ◽

Cutaneous Malignant Melanoma ◽

Metabolic Parameters ◽

Whole Body ◽

Optimal Cutoff ◽

Cutoff Values ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Purpose: The purpose of this study was to investigate the prognostic relevance of metabolic parameters measured using 18F-FDG PET/CT in patients with metastatic cutaneous malignant melanoma (CMM).Materials and Methods: The prognostic impact of whole-body metabolic tumor volume (wMTV), whole-body tumor lesion glycolysis (wTLG), maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) was evaluated in 42 metastatic CMM patients who underwent 18F-FDG PET/CT. The metabolic parameters were dichotomized by optimal cutoff values using time-dependent receiver operating characteristic (ROC) curves. In addition, univariate and multivariate analyses of the metabolic parameters were performed using the Kaplan-Meier method and Cox proportional hazards models.Results: The optimal cutoff values for disease-free survival (DFS) were 4.63 for SUVmax, 3.31 for SUVmean, 8.22 cm3 for wMTV, and 18.22 for wTLG. The optimal cutoff values for melanoma-specific survival (MSS) were 4.77 for SUVmax, 3.31 for SUVmean, 22.32 cm3 for wMTV, and 51.37 for wTLG. Thirty-two (72%) of the 42 patients experienced recurrence during the follow-up period, and 21 patients (50%) died from the disease. In univariate analysis, SUVmax greater than 4.63 (p= 0.025) and SUVmean greater than 3.31 (p= 0.011) affected DFS, while SUVmax greater than 4.77 (p= 0.039), wMTV greater than 22.32 (p= 0.023) and wMTV greater than 51.37 (p= 0.016) affected MSS. In multivariate analysis after adjustment for the effects of clinical parameters, SUVmax was the best predictive factor for DFS (p = 0.016), and SUVmax, wMTV and wTLG were the best predictive factors for MSS (p = 0.023, p = 0.018, and p = 0.007).Conclusions: SUVmax appears to be a strong independent prognostic factor for recurrence in metastatic CMM, and SUVmax, wMTV and wTLG were found to be the best predictive markers for melanoma-specific death.

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LINC01140 promotes the progression and tumor immune escape in lung cancer by sponging multiple microRNAs

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002746 ◽

2021 ◽

Vol 9 (8) ◽

pp. e002746

Author(s):

Rongmu Xia ◽

Guojun Geng ◽

Xiuyi Yu ◽

Zhong Xu ◽

Jing Guo ◽

...

Keyword(s):

Lung Cancer ◽

Immune Escape ◽

Direct Interaction ◽

Cell Counting ◽

Tumor Xenograft ◽

Migration And Invasion ◽

Tumor Immune Escape ◽

Expression Levels ◽

Immunodeficient Mice

BackgroundLong intergenic non-protein coding RNA 1140 (LINC01140), a long non-coding RNA, is highly expressed in various cancers; however, its biological functions in lung cancer (LC) progression and immune escape are still unclear.MethodsHere, to elucidate LINC01140 function, 79 paired LC and paracancerous tissues were collected. LINC01140 expression levels were determined using fluorescence in situ hybridization and qPCR analysis. Cell counting kit-8 (CCK-8) assay and transwell assays were performed. The interaction between microRNAs (miRNAs) and LINC01140 was confirmed using an RNA immunoprecipitation assay. Cytokine-induced killer (CIK) cell phenotypes were analyzed by flow cytometry. Cytokine secretion levels were determined by ELISA. CIK cytotoxicity was assessed by measuring lactate dehydrogenase release. Besides, xenograft tumor mouse models were used to unveil the in vivo function of LINC01140.ResultsWe found that LINC01140 was highly expressed in human LC tissues and cell lines. High LINC01140 levels were associated with poor survival in patients with LC. LINC01140 upregulation promoted the proliferation, migration, and invasion of LC cells through direct interaction with miR-33a-5p and miR-33b-5p, thereby contributing to c-Myc expression and also inhibited cisplatin-induced cell apoptosis. In subcutaneous tumor xenograft mice, LINC01140 knockdown markedly reduced tumor growth and lung metastasis. Additionally, LINC01140 directly repressed miR-377-3 p and miR-155-5 p expression levels, resulting in the upregulation of their common downstream target programmed death-ligand 1 (PD-L1), a crucial target in LC immunotherapy. Notably, we proved that LINC01140 knockdown, along with CIK administration, suppressed the growth of subcutaneous LC xenografts by decreasing PD-L1 expression in severe combined immunodeficient mice.ConclusionsTaken together, LINC01140 overexpression protects c-Myc and PD-L1 mRNA from miRNA-mediated inhibition and contributes to the proliferation, migration, invasion, and immune escape of LC cells. These results provide a theoretical basis that LINC01140 is a promising target for LC treatment.

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Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64–labeled daratumumab

Blood Advances ◽

10.1182/bloodadvances.2020002603 ◽

2020 ◽

Vol 4 (20) ◽

pp. 5194-5202

Author(s):

Amrita Krishnan ◽

Vikram Adhikarla ◽

Erasmus K. Poku ◽

Joycelynne Palmer ◽

Ammar Chaudhry ◽

...

Keyword(s):

Multiple Myeloma ◽

Sensitivity And Specificity ◽

Imaging Techniques ◽

Phase 1 ◽

Whole Body ◽

Human Antibody ◽

Whole Body Imaging ◽

Positron Emission ◽

Pet Ct

Abstract 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n = 3), 10 (n = 3), 45 (n = 3), or 95 mg (n = 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.

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Utility of flouro-deoxy-glucose positron emission tomography/computed tomography in the diagnostic and staging evaluation of patients with primary CNS lymphoma

CNS Oncology ◽

10.2217/cns-2019-0016 ◽

2019 ◽

Vol 8 (4) ◽

pp. CNS46 ◽

Cited By ~ 3

Author(s):

Meetakshi Gupta ◽

Tejpal Gupta ◽

Nilendu Purandare ◽

Venkatesh Rangarajan ◽

Ameya Puranik ◽

...

Keyword(s):

Fdg Pet ◽

Standardized Uptake Value ◽

Emission Tomography ◽

Whole Body ◽

Cns Lymphoma ◽

Maximum Standardized Uptake Value ◽

Positron Emission ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Aim: To prospectively assess the clinical utility of pretreatment flouro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients with primary central nervous system (CNS) lymphoma (PCNSL). Materials & methods: Patients with suspected/proven PCNSL underwent baseline whole-body 18F-FDG-PET/CT. Maximum standardized uptake value and tumor/normal tissue ratios were compared between CNS lymphoma and other histological diagnoses. Results: The mean maximum standardized uptake value (27.5 vs 18.2; p = 0.001) and mean tumor/normal tissue ratio (2.34 vs 1.53; p < 0.001) of CNS lymphoma was significantly higher than other histologic diagnoses. Five of 50 (10%) patients with biopsy-proven CNS lymphomas had pathologically increased FDG-uptake at extraneuraxial sites uncovering systemic lymphoma. Conclusion: Pretreatment whole-body 18F-FDG-PET/CT provides valuable complementary information in the diagnostic and staging evaluation of patients with PCNSL to guide therapeutic decision-making.

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Quantitative gene expression underlying 18f-fluorodeoxyglucose uptake in colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.653 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 653-653

Author(s):

Bodil E. Engelmann ◽

Tina Binderup ◽

Andreas Kjær ◽

Annika Loft ◽

Thomas A. Gerds ◽

...

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Fdg Pet ◽

Standardized Uptake Value ◽

Normal Colonic Mucosa ◽

Imaging Method ◽

Glucose Transporter 1 ◽

Expression Levels ◽

Pet Ct ◽

Gene Expression Levels

653 Background: Positron emission tomography (PET) with the glucose analogue 18F-fluorodeoxyglucose (FDG) is widely used in oncologic imaging. This study examines the molecular mechanism underlying the detection of colon cancer (CC) by FDG-PET. Methods: Pre-operative PET/CT scans and tissue samples from primary CC and surrounding normal mucosa were obtained from 42 patients. FDG uptake was quantified using maximal standardized uptake value (SUVmax). The expression of ki67, glucose transporter 1 (GLUT-1), hexokinase 1 (HK1), hexokinase 2 (HK2), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF1α) and carbonic anhydrase IX (CaIX) mRNA was examined by quantitative real time reverse transcriptase-polymerase chain reaction. Results: All primary tumours showed increased uptake of FDG. The mean SUVmax was 15.0 (range 5.3 – 37.8). No correlation was found between tumour size and SUVmax. Mean gene expression levels of GLUT1, HK2, ki67, HIF1α, VEGF and CaIX, but not HK1, were significantly higher in primary tumours than in surrounding normal colonic mucosa. Linear regressions pairing tumour SUVmax with gene expression levels showed significant correlations between SUVmax and HK2, ki67 and CaIX, respectively. Conclusions: These results confirm FDG PET/CT as a functional imaging method in CC, and that FDG accumulation reflects molecular events related to glycolysis, cell proliferation, hypoxia, but not angiogenesis.

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