Targeted Molecular Imaging of Translocator Protein (TSPO) Using ^18FGE180-PET for the Diagnosis of Gastrointestinal Graft Versus host Disease (GI-GVHD)

Introduction:

Acute Gastrointestinal Graft Versus Host Disease (GI-GVHD) is a life-threatening complication following haematopoietic progenitor cell transplantation (HPCT). Recent data suggest that the current gold standard diagnostic test (endoscopic biopsy) fails to identify 26% of those patients requiring treatment. The mitochondrial translocator protein TSPO is upregulated in activated macrophages and inflammatory bowel diseases, and thus may be a biomarker of acute GI-GVHD. ^18FGE180 is a novel TSPO-targeting radioligand for use in positron emission tomography imaging (^18FGE180-PET).

Methods:

We performed a prospective observational pilot study evaluating ^18FGE180-PET in adults with clinically suspected acute GI-GVHD occurring within 100 days following HPCT. Participants underwent a baseline ^18FGE180-PET within 7 days of diagnostic endoscopy, and a follow-up ^18FGE180-PET 1-4 weeks later. Tissue avidity was assessed visually in four sections of the gastrointestinal tract (GIT; stomach, duodenum, sigmoid and rectum) and rated by standardised uptake variable (SUV), with "positive" defined by SUV greater than mediastinal blood pool (MBP). Imaging findings were correlated with patient demographics, symptom severity (defined by modified Glucksberg stage), endoscopic findings, and histologic diagnosis. For patients in whom GI-GVHD treatment was initiated (defined as minimum prednisone 1mg/kg or equivalent), the clinical response was correlated with GIT avidity during the second ^18FGE180-PET.

Results:

Six (6) patients were recruited, with median age 57 years (range 53-68 years), at a median 66 days post HPCT (range 26-95 days). Median Glucksberg stage of presumptive GI-GVHD was 2 (range 1-3). The histological diagnosis was GI-GVHD in 4 (66%) patients, and drug toxicity in the remaining two patients. Concordance between histological findings and ^18FGE180-PET avidity by GIT section were 50% (stomach), 100% (duodenum), 100% (sigmoid) and 80% (rectum). ^18FGE180-PET was highly accurate in duodenum and sigmoid (sensitivity 100%, specificity 100%), moderately accurate in rectum (sensitivity 66%, specificity 100%), and non-specific in stomach (sensitivity 100%, specificity 25%). Five (83%) patients subsequently underwent treatment for GI-GVHD, and of these 4 (80%) underwent repeat ^18FGE180-PET for response assessment, seven days after the first. In these patients, high concordance between clinical response and ^18FGE180-PET avidity was demonstrated in sigmoid (100%), rectum (100%) and duodenum (75%), compared with poor concordance in stomach (25%). The final patient, whose biopsies were negative for GI-GVHD and did not undergo GVHD treatment, was non-avid at all sites on both initial and subsequent ^18FGE180-PET.

Conclusion:

^18FGE180-PET appears to show utility in the diagnosis of GI-GVHD in small and large bowel. Larger prospective studies, correlating with histological TSPO expression, are warranted.