RT Journal Article
SR Electronic
T1 Preclinical SPECT/CT Imaging of αvβ6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 2146
OP 2152
DO 10.2967/jnumed.113.120592
VO 54
IS 12
A1 Alison E. John
A1 Jeni C. Luckett
A1 Amanda L. Tatler
A1 Ramla O. Awais
A1 Ami Desai
A1 Anthony Habgood
A1 Steve Ludbrook
A1 Andy D. Blanchard
A1 Alan C. Perkins
A1 R. Gisli Jenkins
A1 John F. Marshall
YR 2013
UL http://jnm.snmjournals.org/content/54/12/2146.abstract
AB Transforming growth factor β activation by the αvβ6 integrin is central to the pathogenesis of idiopathic pulmonary fibrosis. Expression of the αvβ6 integrin is increased in fibrotic lung tissue and is a promising therapeutic target for treatment of the disease. Currently, measurement of αvβ6 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 αvβ6 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 111In-labeled αvβ6-specific (diethylenetriamine pentaacetate-tetra [DTPA]-A20FMDV2) or control (DTPA-A20FMDVran) peptide by nanoSPECT/CT imaging. Development of fibrosis was assessed by lung hydroxyproline content, and αvβ6 protein and itgb6 messenger RNA were measured in the lungs. Results: Maximal binding of 111In-labeled A20FMDV2 peptide to αvβ6 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 αvβ6-blocking antibodies. Levels of 111In-labeled A20FMDV2 peptide correlated positively with hydroxyproline, αvβ6 protein, and itgb6 messenger RNA levels. Conclusion: We have developed a highly sensitive, quantifiable, and noninvasive technique for measuring αvβ6 integrin levels within the lung. Measurement of αvβ6 integrins by SPECT/CT scanning has the potential for use in stratifying therapy for patients with pulmonary fibrosis.