To develop a new probe for the αvβ6-integrin and assess its potential for PET imaging of carcinomas.
Ga-68-Trivehexin was synthesized by trimerization of an optimized αvβ6-integrin selective cyclic
nonapeptide on the TRAP chelator core and automated labeling with Ga-68. The tracer was
characterized by ELISA for activities towards integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1, as well as
by cell binding assays on H2009 (αvβ6-positive) and MDA-MB-231 (αvβ6-negative) cells. SCID mice
bearing subcutaneous xenografts of the same cell lines were used for dynamic (90 min) and static
(75 min p.i.) μPET imaging, as well as for biodistribution (90 min p.i.). Structure-activity-relationships
were established by comparison with the predecessor compound Ga-68-TRAP(AvB6)3. Ga-68-
Trivehexin was tested for in-human PET/CT imaging of HNSCC, parotideal adenocarcinoma, and
Ga-68-Trivehexin showed a high αvβ6-integrin affinity (IC50 = 0.033 nM), selectivity over other
subtypes (IC50-based factors: αvβ8, 188; αvβ3, 82; α5β1, 667), blockable uptake in H2009 cells, and
negligible uptake in MDA-MB-231 cells. Biodistribution and preclinical PET imaging confirmed a high
target-specific uptake in tumor and a low non-specific uptake in other organs and tissues except the
excretory organs (kidneys and urinary bladder). Preclinical PET corresponded well to in-human results,
showing high and persistent uptake in metastatic PDAC and HNSCC (SUVmax = 10–13) as well as in
kidneys/urine. Ga-68-Trivehexin enabled PET/CT imaging of small PDAC metastases and showed high
uptake in HNSCC but not in tumor-associated inflammation.
Ga-68-Trivehexin is a valuable probe for imaging of αvβ6-integrin expression in human cancers.