Synthesis and evaluation of 111In‐labeled tetrapeptide‐based compounds as single‐photon emission computed tomography imaging probes targeting granzyme B

Abstract

Granzyme B is an attractive target as a biomarker for contributing to improve the treatment with immune checkpoint inhibitor (ICI). In this study, we designed novel 111In‐labeled granzyme B‐targeting single‐photon emission computed tomography (SPECT) imaging probes, [111In]IDT and [111In]IDAT. Nonradioactive In‐labeled granzyme B‐targeting compounds ([natIn]IDT, [natIn]IDAT) showed the affinity for recombinant mouse granzyme B. [111In]IDT and [111In]IDAT were obtained with moderate radiochemical yield and high stability in mouse plasma (>95%). In a biodistribution experiment using tumor‐bearing mice, [111In]IDT and [111In]IDAT showed moderate accumulation in tumor. Ex vivo autoradiography (ARG) indicated that the accumulation of radioactivity in tumor was correlated to expression of granzyme B confirmed by the immunohistochemical staining. These results indicated that [111In]IDT and [111In]IDAT showed the basic properties as granzyme B‐targeting SPECT probes.