Imaging FIB ONE in the Human Lung Using Endomicroscopy

While the process of fibrosis is essential for normal wound healing, an excessive and uncontrolled 'fibrotic' response can result in impaired tissue structure and function. In other words, affected 'fibrotic' tissues are unable to heal back to normal and therefore don't work as effectively as they normally would. In the case of the lung, fibrosis can occur across large parts of the lung such as in conditions like Idiopathic Pulmonary Fibrosis (IPF) and sarcoidosis or it can occur in much smaller patches such as around the borders of some lung tumours. At the moment the investigators don't fully understand the mechanisms of fibrosis and so therefore cannot monitor or treat these conditions as effectively as the investigators could. Despite the significant global financial burden of these diseases, treatment options are very limited and monitoring of disease progression remains a real challenge. In an effort to address this problem, the research group are currently developing a library of novel optical molecular imaging SmartProbes that are targeted against key pathological processes in the human lung. The functional profile for this portfolio of probes is that they exhibit high stability and specificity in vivo and have a short activation time permitting rapid point-of-care in situ molecular profiling enabling in the future, improved diagnostic certainty and stratification for targeted pharmacological intervention. This clinical microdosing study protocol focuses around the intrapulmonary delivery of microdoses (\<100µg) of the Smartprobe Fibroproliferation (FIB ONE) to disparate regions of the human lung to highlight MMP activity combined with an active MMP inhibitor (AZD1236) to the distal lung. This approach will enable the research team to directly demonstrate the utility of this SmartProbe-based platform in the validation of drug target engagement in areas of suspected fibroproliferation (characterised by increased MMP activity).

Sex

All

Minimum age

16 Years

Inclusion Criteria:

All Cohorts Capacity to provide informed consent

* ≥ 16 years
* Attending consultant permission for bronchoscopy
* Thoracic CT scan taken within the previous 10 weeks
* Readily accessible target areas with bronchoscopy and FE
* Cohort 1 - Patients with a suspected or confirmed lung condition associated with increased activity of the fibroproliferative pathway and scheduled to undergo an elective bronchoscopy
* Cohort 2 - Patients undergoing planned cardiothoracic surgery for biopsy/resection of a lung condition associated with increased activity of the fibroproliferative pathway.

Exclusion Criteria:

* All Cohorts
* Refusal for participation by attending consultant
* Any history of anaphylaxis
* Significant coagulopathy or bleeding tendency, which causes bronchoscopy to be unsuitable, as determined by clinical co-investigator or the participant's attending consultant, using information which is routinely available
* Myocardial infarction in the preceding four weeks
* Women who are pregnant or are breastfeeding
* Receiving drugs that cause increased autofluorescence in the lung, specifically amiodorane and methotrexate