18F-Fluorodeoxyglucose positron emission tomography pulmonary imaging in idiopathic pulmonary fibrosis is reproducible: implications for future clinical trials

Win, Thida; Lambrou, Tryphon; Hutton, Brian; Kayani, Irfan; Screaton, Nicholas; Porter, Joanna C.; Maher, Toby M.; Endozo, Raymondo; Shortman, Robert I.; Lukey, Pauline T.; Groves, Ashley M.

doi:10.1007/s00259-011-1986-7

Cited by 46 publications

(45 citation statements)

References 33 publications

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“…The 111 In-DTPA-A20FMDV2 is known to bind to human avb6 integrins in vitro and in vivo (30,31) and 111 In-labeled peptides are widely used in clinical practice. Moreover, 18 F-A20FMDV2 has been used in vivo for successful PET imaging of avb6 on human xenografts (30), and PET/CT scans have previously been obtained for IPF patients (22,23). Thus, SPECT/CT or PET/CT with radiolabeled A20FMDV2 can offer valuable new imaging modalities for stratifying patients with IPF, although at the present time SPECT is more widely available and less costly than PET imaging.…”

Section: Discussionmentioning

confidence: 99%

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Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

et al. 2013

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Transforming growth factor b activation by the avb6 integrin is central to the pathogenesis of idiopathic pulmonary fibrosis. Expression of the avb6 integrin is increased in fibrotic lung tissue and is a promising therapeutic target for treatment of the disease. Currently, measurement of avb6 integrin levels in the lung requires immunohistochemical analysis of biopsy samples. This procedure is clinically impractical for many patients with pulmonary fibrosis, and a noninvasive strategy for measuring avb6 integrin levels in the lungs is urgently required to facilitate monitoring of disease progression and therapeutic responses. Methods: Using a murine model of bleomycin-induced lung injury, we assessed the binding of intravenously administered 111 In-labeled avb6-specific (diethylenetriamine pentaacetate-tetra [DTPA]-A20FMDV2) or control (DTPAA20FMDVran) peptide by nanoSPECT/CT imaging. Development of fibrosis was assessed by lung hydroxyproline content, and avb6 protein and itgb6 messenger RNA were measured in the lungs. Results: Maximal binding of 111 In-labeled A20FMDV2 peptide to avb6 integrins was detected in the lungs 1 h after intravenous administration. No significant binding was detected in mice injected with control peptide. Integrin binding was increased in the lungs of bleomycin-, compared with saline-, exposed mice and was attenuated by pretreatment with avb6-blocking antibodies. Levels of 111 In-labeled A20FMDV2 peptide correlated positively with hydroxyproline, avb6 protein, and itgb6 messenger RNA levels. Conclusion: We have developed a highly sensitive, quantifiable, and noninvasive technique for measuring avb6 integrin levels within the lung. Measurement of avb6 integrins by SPECT/CT scanning has the potential for use in stratifying therapy for patients with pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 99%

“…Initial studies have used PET tracers including 18 F-FDG and 68 Ga-labeled somatostatin analogs that bind the somatostatin receptor (21,22). Pulmonary uptake of both these radiotracers is increased in IPF patients, and lung 18 F-FDG levels have been related to disease severity (23).…”

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confidence: 99%

Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

et al. 2013

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“…A few recent studies evaluated the use of PET techniques in IPF patients (7)(8)(9)(10)(11)(12)(13)(14)(15), mostly with 18 F-FDG as a tracer of glucose uptake and metabolism. These studies showed that lungs from IPF patients present a clear enhancement of 18 F-FDG uptake, with an excellent short-term reproducibility (11)(12)(13)(14).…”

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confidence: 99%

“…These studies showed that lungs from IPF patients present a clear enhancement of 18 F-FDG uptake, with an excellent short-term reproducibility (11)(12)(13)(14). However, it is actually not known whether 18 F-FDG uptake is related to the severity of the fibrotic process and could be exploited for early assessment of antifibrotic therapies.…”

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confidence: 99%

PET/CT with ¹⁸F-FDG– and ¹⁸F-FBEM–Labeled Leukocytes for Metabolic Activity and Leukocyte Recruitment Monitoring in a Mouse Model of Pulmonary Fibrosis

et al. 2014

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Idiopathic pulmonary fibrosis is characterized by a progressive and irreversible respiratory failure. Validated noninvasive methods able to assess disease activity are essential for prognostic purposes as well as for the evaluation of emerging antifibrotic treatments. Methods: C57BL/6 mice were used in a murine model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin (control mice were instilled with a saline solution). At different times after instillation, PET/CT with 18 F-FDG-or 18 F-4-fluorobenzamido-Nethylamino-maleimide ( 18 F-FBEM)-labeled leukocytes was performed to assess metabolic activity and leukocyte recruitment, respectively. Results: In bleomycin-treated mice, a higher metabolic activity was measured on 18 F-FDG PET/CT scans from day 7 to day 24 after instillation, with a peak of activity measured at day 14. Of note, lung mean standardized uptake values correlated with bleomycin doses, histologic score of fibrosis, lung hydroxyproline content, and weight loss. Moreover, during the inflammatory phase of the model (day 7), but not the fibrotic phase (day 23), bleomycin-treated mice presented with an enhanced leukocyte recruitment as assessed by 18 F-FBEM-labeled leukocyte PET/CT. Autoradiographic analysis of lung sections and CD45 immunostaining confirm the higher and early recruitment of leukocytes in bleomycin-treated mice, compared with control mice. Conclusion: 18 F-FDG-and 18 F-FBEM-labeled leukocyte PET/CT enable monitoring of metabolic activity and leukocyte recruitment in a mouse model of pulmonary fibrosis. Implications for preclinical evaluation of antifibrotic therapy are expected.

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“…Metabolically (specifically, glycolysis) active cells have a higher rate of 18 F-FDG uptake and therefore have a higher accumulation of 18 F-FDG, which distinguishes them from quiescent normal cells on PET scans. 18 F-FDG PET is a sensitive imaging modality for the detection of cellular glucose uptake in rabbit models of lung inflammation and fibrosis as well as in human IPF (32,33). PET scans have shown that lung uptake of 18 F-FDG after intravenous injection was increased in microcrystalline silica-or BLM-treated rabbits compared with control rabbits, and the 18 F-FDG signals persisted for several weeks in the lung (34).…”

Section: Nuclear Imaging and Multimodality Imagingmentioning

confidence: 99%

Noninvasive Imaging of Experimental Lung Fibrosis

Zhou

Chen

Ambalavanan³

et al. 2015

Am J Respir Cell Mol Biol

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18F-Fluorodeoxyglucose positron emission tomography pulmonary imaging in idiopathic pulmonary fibrosis is reproducible: implications for future clinical trials

Abstract: This study demonstrated that there is excellent short-term reproducibility in pulmonary (18)F-FDG uptake in patients with IPF.

Cited by 46 publications

References 33 publications

Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

PET/CT with ¹⁸F-FDG– and ¹⁸F-FBEM–Labeled Leukocytes for Metabolic Activity and Leukocyte Recruitment Monitoring in a Mouse Model of Pulmonary Fibrosis

Noninvasive Imaging of Experimental Lung Fibrosis

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18F-Fluorodeoxyglucose positron emission tomography pulmonary imaging in idiopathic pulmonary fibrosis is reproducible: implications for future clinical trials

Abstract: This study demonstrated that there is excellent short-term reproducibility in pulmonary (18)F-FDG uptake in patients with IPF.

Cited by 46 publications

References 33 publications

Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

PET/CT with 18F-FDG– and 18F-FBEM–Labeled Leukocytes for Metabolic Activity and Leukocyte Recruitment Monitoring in a Mouse Model of Pulmonary Fibrosis

Noninvasive Imaging of Experimental Lung Fibrosis

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PET/CT with ¹⁸F-FDG– and ¹⁸F-FBEM–Labeled Leukocytes for Metabolic Activity and Leukocyte Recruitment Monitoring in a Mouse Model of Pulmonary Fibrosis