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

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.