Gene Expression Patterns and Tumor Uptake of18F-FDG,18F-FLT, and18F-FEC in PET/MRI of an Orthotopic Mouse Xenotransplantation Model of Pancreatic Cancer

Forstner, Corinna von; Egberts, Jan‐Hendrik; Ammerpohl, Ole; Niedzielska, Dagmara; Buchert, Ralph; Mikecz, Pál; Schumacher, Udo; Peldschus, Kersten; Adam, Gerhard; Pilarsky, Christian; Grützmann, Robert; Kalthoff, Holger; Henze, Eberhard; Brenner, Winfried

doi:10.2967/jnumed.107.050021

Cited by 40 publications

(18 citation statements)

References 29 publications

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“…Smith-Jones et al (28) showed that 18 FDG-PET may be limited in detecting the cytostatic response to targeted therapies because of its lack of specificity. This could lead to the use of a more specific marker of cell proliferation, such as 3-deoxy-3-18 F-fluorothymidine (29). Indeed, Atkinson et al (30) reported that 3-deoxy-3-18 F-fluorothymidine allowed anti-EGFR inhibitor therapy in squamous cell carcinoma to be monitored.…”

Section: Discussionmentioning

confidence: 99%

Preclinical and Clinical Evidence that Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography with Computed Tomography Is a Reliable Tool for the Detection of Early Molecular Responses to Erlotinib in Head and Neck Cancer

Vergez

Delord

Thomas

et al. 2010

Clinical Cancer Research

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Purpose: There is a clinical need to identify predictive markers of the responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography with computed tomography ( 18 FDG-PET/CT) could be a tool of choice for monitoring the early effects of this class of agent on tumor activity.Experimental Design: Using models of human head and neck carcinoma (CAL33 and CAL166 cell lines), we first tested in vitro and in vivo whether the in vivo changes in 18 FDG-PET/CT uptake were associated with the molecular and cellular effects of the EGFR-TKI erlotinib. Then, the pathologic and morphologic changes and the 18 FDG-PET/CT uptake before and after erlotinib exposure in patients were analyzed.Results: Erlotinib strongly inhibited extracellular signal-regulated kinase-1/2 (ERK-1/2) phosphorylation both in the preclinical models and in patients. Western blotting, immunofluorescence, and immunohistochemistry showed that erlotinib did not modify Glut-1 expression at the protein level either in cell line models or in tumor tissue from mouse xenografts or in patients. Phospho-ERK-1/2 inhibition was associated with a reduction in 18 FDG uptake in animal and human tumors. The biological volume was more accurate than the standardized uptake value for the evaluation of the molecular responses.Conclusion: These results show that the 18 FDG-PET/CT response is a reliable surrogate marker of the effects of erlotinib in head and neck carcinoma. Clin Cancer Res; 16(17); 4434-45. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Preclinical and Clinical Evidence that Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography with Computed Tomography Is a Reliable Tool for the Detection of Early Molecular Responses to Erlotinib in Head and Neck Cancer

Vergez

Delord

Thomas

et al. 2010

Clinical Cancer Research

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“…Thus, two 18 F-labeled derivates of 11 C-choline, 18 F-fluoroethylcholine (FEC) and 18 F-fluorocholine (FCh), have been developed. These tracers supposedly have in vivo biodistribution and pharmacokinetics similar to 11 C-choline (22,23). Although 18 F-FEC and 18 F-FCh show similar clinical results to choline and have the advantage of a 2-h halflife, their renal clearance and subsequent high degree of bladder activity rely on PET/CT.…”

mentioning

confidence: 99%

Assessment of PET Tracer Uptake in Hormone-Independent and Hormone-Dependent Xenograft Prostate Cancer Mouse Models

Kukuk¹,

Reischl²,

Raguin³

et al. 2011

J Nucl Med

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The pharmacokinetics of 18 F-fluorodeoxythymidine (FLT), 18 F-FDG, 11 C-choline, and 18 F-fluoroethylcholine (FEC) in 2 hormoneindependent (PC-3, DU145) and 2 hormone-dependent (CWR22, PAC120) prostate cancer xenograft mouse models were evaluated by PET and compared by immunohistochemistry. Further investigation was performed to determine whether PET can detect early changes in tumor metabolism after androgen ablation therapy through surgical castration. Methods: PET was performed on 4 consecutive days. In addition, the CWR22 and PAC120 tumor models were surgically castrated after the baseline measurement and imaged again after castration. The tracer uptake was analyzed using time-activity curves, percentage injected dose per volume (%ID/cm 3 ), and tumor-to-muscle ratio (T/M). Results: Regarding the hormone-independent prostate tumor models, 18 F-FLT showed the best T/M and highest %ID/cm 3 in PC-3 (2.97 6 0.63 %ID/cm 3 ) and DU145 (2.06 6 0.75 %ID/cm 3 ) tumors. 18 F-FDG seemed to be the tracer of choice for delineation of the PC-3 tumors but not for the DU145 tumors. Using 11 C-choline (PC-3: 1.33 6 0.29 %ID/cm 3 , DU145: 1.60 6 0.27 %ID/cm 3 ) and 18 F-FEC, we did not find any significant uptake in the tumors, compared with muscle tissue. Regarding the hormone-dependent prostate tumor models, the CWR22 model showed a highly significant (P , 0.01) decrease in tumor 18 F-FDG uptake from 4.11 6 1.29 % ID/cm 3 to 2.19 6 1.45 %ID/cm 3 after androgen ablation therapy. However, the 18 F-FLT, 11 C-choline, or 18 F-FEC tracers did not provide sufficient uptake or reliable information about therapy response in CWR22 tumors. The PAC120 model showed a significant increase in 18 F-FLT tumor uptake (P 5 0.015) after androgen ablation therapy. The accumulation of 18 F-FEC (before: 2.32 6 1.01 %ID/cm 3 , after: 1.36 6 0.39 %ID/cm 3 ) was found to be the next highest after 18 F-FDG (before: 2.45 6 0.93 %ID/cm 3 , after: 2.18 6 0.65 %ID/cm 3 ) in PAC120 tumors before castration and is better suited for monitoring therapy response. Conclusion: This comprehensive study in 2 hormone-dependent and 2 hormone-independent prostate tumor mouse models shows that 18 F-FLT and 18 F-FDG are the most appropriate tracers for delineation of PC-3, DU145 (except 18 F-FDG), and CWR22 tumors, but not for PAC120 tumors. 18 F-FEC and 11 Ccholine, in particular, revealed insufficient T/M ratio in the prostate tumor models. The results may indicate that radiolabeled choline and choline derivatives compete with a high concentration of the precursor dimethylaminoethanol, resulting in reduced uptake in small-rodent tumor models, a hypothesis that is currently under investigation in our laboratory.

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“…It is taken up by rapidly proliferating cells and, after phosphorylation, is trapped within cytosol (Fig 20). In a preclinical study by von Forstner et al (96) of radiotracers in severe combined immunodeficient (SCID) mice in 2008, it was reported that 18 F FLT had the highest and most consistent uptake (evaluated with an MR imaging scanner) of various human pancreatic tumor cell lines compared with 18 F FDG and 18 F fluorethylcholine (FEC). In recent years, other preclinical studies have evaluated the ability of FLT to depict response to anticancer treatments, reporting early reductions in cellular FLT uptake after radio-and chemotherapy (97).…”

Section: Recent Developments In Pet Novel Radiotracersmentioning

confidence: 97%

State-of-the-Art PET/CT of the Pancreas: Current Role and Emerging Indications

Sahani¹,

Bonaffini²,

Catalano³

et al. 2012

RadioGraphics

104

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Fused positron emission tomography (PET)/computed tomography (CT) is a recently developed technology that couples the functional information of PET with the anatomic details of CT. Integrated PET/CT scanners produce both PET and contrast material-enhanced CT images of the entire body in one setting. Typically, the amount of fluorine 18 (F-18) fluorodeoxyglucose (FDG) uptake in normal pancreatic parenchyma is insignificant compared with that of the liver. However, both malignant (eg, adenocarcinoma) and benign (eg, acute pancreatitis) pancreatic conditions may demonstrate intense FDG uptake. PET/CT provides an opportunity to depict pancreatic tumors and distant metastases, perform preoperative staging, and monitor response to treatment, and it has proved useful in distinguishing postoperative fibrosis from recurrence. In selected cases, PET/CT findings may be used to help diagnose autoimmune pancreatitis mimicking a mass by depicting systemic involvement. PET/CT may also be used to direct biopsy to sites more likely to yield representative tumor tissue. Novel radiolabeled molecules, such as sigma-receptor ligands and F-18-3'-fluoro-3'-deoxy-l-thymidine (FLT), may play an even greater role in distinguishing tumor recurrence from postoperative fibrosis or inflammation. (C)RSNA, 2012 . radiographics.rsna.or

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Gene Expression Patterns and Tumor Uptake of¹⁸F-FDG,¹⁸F-FLT, and¹⁸F-FEC in PET/MRI of an Orthotopic Mouse Xenotransplantation Model of Pancreatic Cancer

Cited by 40 publications

References 29 publications

Preclinical and Clinical Evidence that Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography with Computed Tomography Is a Reliable Tool for the Detection of Early Molecular Responses to Erlotinib in Head and Neck Cancer

Preclinical and Clinical Evidence that Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography with Computed Tomography Is a Reliable Tool for the Detection of Early Molecular Responses to Erlotinib in Head and Neck Cancer

Assessment of PET Tracer Uptake in Hormone-Independent and Hormone-Dependent Xenograft Prostate Cancer Mouse Models

State-of-the-Art PET/CT of the Pancreas: Current Role and Emerging Indications

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