Chemical design of radioiodinated probes with a metabolizable linkage for target-selective imaging of systemic amyloidosis.

Introduction: Systemic amyloidosis is a rare disease caused by the deposition of amyloid fibrils in various organs. Amyloid-targeted radiopharmaceuticals have been developed and applied to diagnose systemic amyloidosis peripherally; however, high-contrast imaging has not been achieved because of the high background signals in normal organs. To overcome this problem, we designed an amyloid-targeted radioiodinated probe 1 with a metabolizable linkage (ester bond) to release of radiolabeled metabolites (m-iodohippuric acid) in normal organs that could be rapidly excreted in the urine.
Methods: Compound 1 was synthesized by conjugating 2-(4-(methylamino)phenyl)benzo[d]thiazol-6-ol, an amyloid-targeting compound, with m-iodohippuric acid. [ ¹²⁵ I]1 was synthesized via iododestannylation using a tributyltin precursor. Mouse models of amyloid A (AA) amyloidosis, a type of systemic amyloidosis, were prepared by administering amyloid-enhancing factor to mice and used for in vitro autoradiography using organ sections and in vivo evaluation.
Results: [ ¹²⁵ I]1 was obtained with a radiochemical yield of 59% and radiochemical purity of over 95%. An in vitro autoradiographic study demonstrated that [ ¹²⁵ I]1 specifically binds to amyloid in the splenic tissue. Upon administration to normal mice, [ ¹²⁵ I]1 was distributed to organs throughout the body, followed by the rapid excretion of radioactivity in the urine as m-[ ¹²⁵ I]iodohippuric acid. Furthermore, ex vivo autoradiography showed that [ ¹²⁵ I]1 bound to the amyloid formed around the follicles in the spleens of AA amyloidosis model mice.
Conclusion: These results suggest that the interposition of a metabolizable linkage between an amyloid-targeting moiety and a radiolabeled hippuric acid would be useful in the design of radiopharmaceuticals for high-contrast imaging of systemic amyloidosis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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