[18F]-fluoroestradiol quantitative PET imaging to differentiate ER+ and ERα-knockdown breast tumors in mice

Paquette, Michel; Ouellet, René; Archambault, Mélanie; Croteau, Étienne; Bénard, François

doi:10.1016/j.nucmedbio.2011.06.004

Cited by 17 publications

(15 citation statements)

References 24 publications

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“…However, it was not clear which subtype of ER exerts the biologic effect on the tumors. It was also reported that the absolute binding affinity of 18 F-FES was 6.3-fold greater for ERa than for ERb, and thus 18 F-FES uptake mainly reflects the expression of ERa, which reliably differentiates tumors with ERa expression from those with less ERa expression in vivo (20,21). In the present study, significant agreement was found between 18 F-FES uptake and the ERa immunohistochemistry score (r 5 0.48 and 0.78 in leiomyoma and sarcoma, respectively), although the mean of 18 F-FES SUV in sarcoma was significantly lower than that in leiomyoma.…”

Section: Discussionmentioning

confidence: 99%

¹⁸F-FES and ¹⁸F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

et al. 2013

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The aim of this study was to investigate the relationship between the tumor uptake of 16a-18 F-fluoro-17b-estradiol ( 18 F-FES) and 18 F-FDG using PET and expressions of sex hormone receptors, such as estrogen receptor (ER), as well as glucose transporter 1 (GLUT-1) and Ki-67 analyzed by the immunohistochemistry method in mesenchymal uterine tumors. Methods: Forty-seven patients with mesenchymal uterine tumors were studied with 18 F-FES and 18 F-FDG PET. Postoperative pathologic diagnosis revealed 33 uterine leiomyomas and 14 uterine sarcomas. Tissue samples were assayed for expression of ERa, ERb, progesterone receptor (PR), PR-B, GLUT-1, and Ki-67 by an immunohistochemistry method. Standardized uptake values (SUVs) for 18 F-FES and 18 F-FDG were compared with the semiquantitative immunoreactive score (0-12) and quantitative labeling index (LI) for Ki-67 in immunohistochemistry. Results: 18 F-FES uptake was significantly lower (P , 0.001) and the 18 F-FDG uptake and SUV ratio of 18 F-FDG to 18 F-FES ( 18 F-FDG/ 18 F-FES ratio) (P , 0.005 and P , 0.001, respectively) were significantly higher in uterine sarcomas than in leiomyomas. Immunohistochemistry analysis showed significantly higher expressions of ERa, PR, and PR-B in uterine leiomyomas than in sarcomas. The Ki-67 LI was significantly greater in uterine sarcomas than in leiomyomas. Correlation analysis for all tumors showed positive correlations between 18 F-FES SUV and immunohistochemistry scores of ERa, PR (P , 0.001), and PR-B (P , 0.005) as well as between 18 F-FDG SUV and GLUT-1 and Ki-67 (P , 0.001). However, the 18 F-FDG/ 18 F-FES ratio showed significantly negative correlations with ERa, PR (P , 0.001), and PR-B (P , 0.005) and a positive correlation with Ki-67 LI (P , 0.001). In uterine sarcomas, ERa and 18 F-FES SUV showed a positive correlation (P , 0.001) in a low SUV range, and the 18 F-FDG/ 18 F-FES ratio showed positive correlations with ERb and GLUT-1 expression (P , 0.005). Conclusion: 18 F-FES and 18 F-FDG PET showed correlations between tracer uptake and expressions of sex hormone receptors, GLUT-1, and Ki-67 in mesenchymal uterine tumors. The 18 F-FDG/ 18 F-FES ratio was correlated with Ki-67, GLUT-1, and ERb in uterine sarcoma. Functional PET imaging and PET parameters would be useful noninvasive biomarkers for the assessment of tumor hormone receptor expression, glucose metabolism, and proliferation and for differential diagnosis of uterine leiomyoma and sarcoma.

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Section: Discussionmentioning

confidence: 99%

¹⁸F-FES and ¹⁸F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

et al. 2013

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“…This finding is an important factor that explains the relatively low magnitude of variation between the SUV max of healthy and cancerous bones. Statistical variability could be reduced using SUV 4max (a variation of SUV max ) (33).…”

Section: Discussionmentioning

confidence: 99%

Mammary Cancer Bone Metastasis Follow-up Using Multimodal Small-Animal MR and PET Imaging

et al. 2013

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Despite tremendous progress in the management of breast cancer, the survival rate of this disease is still correlated with the development of metastases-most notably, those of the bone. Diagnosis of bone metastasis requires a combination of multiple imaging modalities. MR imaging remains the best modality for soft-tissue visualization, allowing for the distinction between benign and malignant lesions in many cases. On the other hand, PET imaging is frequently more specific at detecting bone metastasis by measuring the accumulation of radiotracers, such as 18 F-sodium fluoride ( 18 F-NaF) and 18 F-FDG. Thus, the main purpose of this study was to longitudinally monitor bone tumor progression using PET/MR image coregistration to improve noninvasive imaging-assisted diagnoses. Methods: After surgical implantation of mammary MRMT-1 cells in a rat femur, we performed minimally invasive imaging procedures at different time points throughout tumor development. The procedure consisted of sequential coregistered MR and PET image acquisition, using gadolinium-diethylenetriaminepentaacetic acid (DTPA) as a contrast agent for MR imaging and 18 F-FDG, 11 C-methionine, and 18 F-NaF as molecular tracers for PET imaging. The animals were then euthanized, and complementary radiologic (micro-CT scans) and histologic analyses were performed. Results: In this preclinical study, we demonstrated that coregistered MR and PET images provide helpful information in a rat mammary-derived bone cancer model. First, MR imaging provided a high-definition anatomic resolution that made the localization of bone resorption and tumor extension detectable between days 9 and 18 after the injection of cancer cells in the medullary channel of the femur. Indeed, the calculation of mean standardized uptake value (SUV mean ) and maximal SUV (SUV max ) in bone and softtissue regions, as defined from the gadolinium-DTPA contrastenhanced MR images, showed 18 F-NaF uptake modifications and increased 18 F-FDG or 11 C-methionine uptake in the bone and surrounding soft tissues. 18 F-FDG and 11 C-methionine were compared in terms of the magnitude of change in their uptake and variability. We observed that 11 C-methionine SUV mean variations in the tumor were more important than those of 18 F-FDG. We also found fewer interindividual variations using SUV mean as a quantitative parameter than SUV max . Conclusion: This preclinical evaluation demonstrated that a PET/MR image coregistration protocol provided a powerful tool to evaluate bone tumor progression in a rat model of bone metastasis and that this protocol could be translated to improve the clinical outcome for metastatic breast cancer management.

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“…12,14−18 However, rapid metabolism of probes by 20-hydroxysteroid dehydrogenase limited the use of these probes in human subjects. 19−21 In addition, PET can be restricted by limited spatial and temporal resolution. 2,19,22 In contrast, MRI has high temporal and spatial resolution without exposing patients to radiation.…”

Section: Introductionmentioning

confidence: 99%

“…19−21 In addition, PET can be restricted by limited spatial and temporal resolution. 2,19,22 In contrast, MRI has high temporal and spatial resolution without exposing patients to radiation. 2 Typically, MRI uses contrast agents to increase local signal intensity by distinguishing tissues or organs that are magnetically similar but histologically distinct.…”

Section: Introductionmentioning

confidence: 99%

Progesterone-Targeted Magnetic Resonance Imaging Probes

Townsend

Moyle-Heyrman

Sukerkar³

et al. 2014

Bioconjugate Chem.

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Determination of progesterone receptor (PR) status in hormone-dependent diseases is essential in ascertaining disease prognosis and monitoring treatment response. The development of a noninvasive means of monitoring these processes would have significant impact on early detection, cost, repeated measurements, and personalized treatment options. Magnetic resonance imaging (MRI) is widely recognized as a technique that can produce longitudinal studies, and PR-targeted MR probes may address a clinical problem by providing contrast enhancement that reports on PR status without biopsy. Commercially available MR contrast agents are typically delivered via intravenous injection, whereas steroids are administered subcutaneously. Whether the route of delivery is important for tissue accumulation of steroid-modified MRI contrast agents to PR-rich tissues is not known. To address this question, modification of the chemistry linking progesterone with the gadolinium chelate led to MR probes with increased water solubility and lower cellular toxicity and enabled administration through the blood. This attribute came at a cost through lower affinity for PR and decreased ability to cross the cell membrane, and ultimately it did not improve delivery of the PR-targeted MR probe to PR-rich tissues or tumors in vivo. Overall, these studies are important, as they demonstrate that targeted contrast agents require optimization of delivery and receptor binding of the steroid and the gadolinium chelate for optimal translation in vivo.

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[18F]-fluoroestradiol quantitative PET imaging to differentiate ER+ and ERα-knockdown breast tumors in mice

Cited by 17 publications

References 24 publications

¹⁸F-FES and ¹⁸F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

¹⁸F-FES and ¹⁸F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

Mammary Cancer Bone Metastasis Follow-up Using Multimodal Small-Animal MR and PET Imaging

Progesterone-Targeted Magnetic Resonance Imaging Probes

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[18F]-fluoroestradiol quantitative PET imaging to differentiate ER+ and ERα-knockdown breast tumors in mice

Cited by 17 publications

References 24 publications

18F-FES and 18F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

18F-FES and 18F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

Mammary Cancer Bone Metastasis Follow-up Using Multimodal Small-Animal MR and PET Imaging

Progesterone-Targeted Magnetic Resonance Imaging Probes

Contact Info

Product

Resources

About

¹⁸F-FES and ¹⁸F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis

¹⁸F-FES and ¹⁸F-FDG PET for Differential Diagnosis and Quantitative Evaluation of Mesenchymal Uterine Tumors: Correlation with Immunohistochemical Analysis