Colitis ImmunoPET: Defining Target Cell Populations and Optimizing Pharmacokinetics

Area of Science:

• Immunology
• Medical Imaging
• Gastroenterology

Background:

• Positron emission tomography (PET) with specific probes offers noninvasive assessment of inflammatory bowel disease (IBD).
• Previous studies showed increased intestinal uptake of a Cu-labeled anti-β7 integrin antibody (FIB504.64) in colitic mice.
• This study evaluated an anti-α4β7 integrin antibody (DATK32) and fragments of FIB504.64 for improved imaging.

Purpose of the Study:

• To evaluate Cu-labeled anti-α4β7 integrin antibody (DATK32) and anti-β7 integrin antibody fragments (F(ab")2, Fab) as PET imaging probes for colitis.
• To compare the efficacy of targeting different β7-expressing lymphocyte populations for IBD detection.
• To identify the most promising imaging agent for IBD diagnosis.

Main Methods:

• Dextran sodium sulfate-induced colitis model in mice.
• Immunoproteins (DATK32, FIB504.64, FIB504.64-F(ab")2, FIB504.64-Fab) labeled with Cu.
• PET data acquisition between 1 and 48 hours post-injection.

Main Results:

• Anti-β7 fragments showed rapid focal uptake in the gut and faster clearance from normal tissues compared to the whole antibody.
• Blood concentrations at 24 hours: DATK32 (23.3% ID/g), FIB504.64 (12.9% ID/g), FIB504.64-F(ab")2 (4.1% ID/g), FIB504.64-Fab (0.62% ID/g).
• Colitis-to-control large intestine uptake ratios: DATK32 (1.38), FIB504.64-F(ab")2 (3.15), FIB504.64-Fab (1.84), FIB504.64 (1.78).

Conclusions:

• Targeting all β7-expressing lymphocytes is more promising for IBD imaging than targeting only α4β7-expressing cells.
• The FIB504.64-F(ab")2 fragment demonstrated the highest differential uptake between colitis and control groups.
• FIB504.64-F(ab")2 is the most promising lead molecule for developing an IBD-specific imaging agent.