Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2.

To evaluate integrin αvβ3 (alpha-v-beta-3)-targeted and somatostatin receptor 2 (SSTR2)-targeted nuclear imaging for the visualisation of interstitial lung disease (ILD). The pulmonary expression of integrin αvβ3 and SSTR2 was analysed in patients with different forms of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. Single photon emission CT/CT (SPECT/CT) was performed on days 3, 7 and 14 after BLM instillation using the integrin αvβ3-targeting Expression of integrin αvβ3 and SSTR2 was substantially increased in human ILD regardless of the subtype. Similarly, in lungs of BLM-challenged mice, but not of controls, both imaging targets were stage-specifically overexpressed. While integrin αvβ3 was most abundantly upregulated on day 7, the inflammatory stage of BLM-induced lung fibrosis, SSTR2 expression peaked on day 14, the established fibrotic stage. In agreement with the findings on tissue level, targeted nuclear imaging using SPECT/CT specifically detected both imaging targets ex vivo and in vivo, and thus visualised different stages of experimental ILD. Our preclinical proof-of-concept study suggests that specific visualisation of molecular processes in ILD by targeted nuclear imaging is feasible. If transferred into clinics, where imaging is considered an integral part of patients' management, the additional information derived from specific imaging tools could represent a first step towards precision medicine in ILD.

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Déclaration de conflit d'intérêts

Competing interests: JS, MBe, MBr, SH, SC, RS, CM, CAF-B and TF have no competing interests to declare. OD had consultancy relationship and/or has received research funding from Actelion, AnaMar, Bayer, Boehringer Ingelheim, ChemomAb, EspeRare Foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sanofi, Sinoxa and UCB in the area of potential treatments of scleroderma and its complications. In addition, OD has a patent mir-29 for the treatment of systemic sclerosis licensed. The real or perceived potential conflicts listed above are accurately stated. BM had grant/research support from AbbVie, Protagen and Novartis, and congress support from Pfizer, Roche and Actelion. In addition, BM has a patent mir-29 for the treatment of systemic sclerosis licensed. The real or perceived potential conflicts listed above are accurately stated.