Shimpei Iikuni

Hypoxic cells dynamically translocate during tumor growth and after radiotherapy. The most desirable direction for therapy targeting hypoxic cells is combining imaging and therapy (theranostics), which may help realize personalized medicine. Here, we conducted cancer radiotheranostics targeting carbonic anhydrase-IX (CA-IX), which is overexpressed in many kinds of hypoxic cancer cells, using low-molecular-weight ¹¹¹In and ⁹⁰Y complexes with a bivalent ureidosulfonamide scaf

²²⁵Ac-based radiotheranostics targeting prostate-specific membrane antigen (PSMA) has induced impressive responses in patients with metastatic castration-resistant prostate cancer. To enhance the therapeutic effects of radioligands labeled with ²²⁵Ac (half-life: 10 days), a radioligand that shows longer tumor retention would be useful. Here, we designed and synthesized a straight-chain PSMA-targeting radioligand, PSMA-DA1, which includes an (iodophenyl)butyric acid derivati

The expression of carbonic anhydrase-IX (CA-IX) in tumors can lead to a poor prognosis; thus, CA-IX has attracted much attention as a target molecule for cancer diagnosis and treatment. An ¹¹¹In-labeled imidazothiadiazole sulfonamide (IS) derivative, [¹¹¹In]In-DO3A-IS1, exhibited marked tumor accumulation but also marked renal accumulation, raising concerns about it producing a low signal/background ratio and a high radiation burden on the kidneys. In this study, four <sup>

Deposition of amyloid aggregates has been regarded as an early stage of amyloidosis progression. An imaging probe that can image amyloid aggregates enables the early diagnosis of amyloidosis and contributes to the development of new medical therapies. High binding affinity for amyloid aggregates is essential to develop a useful molecular imaging probe. This article describes a new strategy to enhance the binding affinity of imaging agents targeting amyloid aggregates. We designed and synthesized

Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer's disease (AD). We previously reported (99m)Tc-hydroxamamide ((99m)Tc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1-42)) aggregates present frequently in the form in AD. In this article, we

Carbonic anhydrase IX (CA-IX) is regarded as a favorable target for in vivo imaging because of its specific expression in hypoxic regions of tumors. Hypoxia assists tumor propagation and growth and is resistant to chemotherapy and radiotherapy. Here, we designed and synthesized [^99mTc]hydroxamamide ([^99mTc]Ham) and [^99mTc]methyl-substituted-hydroxamamide ([^99mTc]MHam) complexes including a bivalent CA-IX ligand, sulfonamide (SA), and ureidosulfonamide

Insulinomas are neuroendocrine tumors that are mainly found in the pancreas. Surgical resection is currently the first-line treatment for insulinomas; thus, it is vital to preoperatively determine their locations. The marked expression of the glucagon-like peptide-1 receptor (GLP-1R) is seen in pancreatic β-cells and almost all insulinomas. Radiolabeled derivatives of exendin-4, a GLP-1R agonist, have been used with nuclear medicine imaging techniques for the <i>in vivo</i> detection of the GLP-

The development of an imaging probe targeting β-amyloid (Aβ) plaques in Alzheimer's disease labeled with technetium-99m, the most commonly used radioisotope for clinical diagnoses, has been strongly anticipated.

Insulinomas are neuroendocrine tumors that are derived from pancreatic β-cells, and they often overexpress the glucagon-like peptide-1 receptor (GLP-1R). Radiolabeled exendin-4 derivatives have been used to noninvasively detect the GLP-1R during the diagnosis and preoperative localization of insulinomas; however, their marked renal accumulation can hinder the imaging of pancreatic tail lesions. In this study, we designed and synthesized ¹¹¹In-labeled exendin-4 derivatives that possess

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid aggregates in the walls of the cerebral vasculature. Recently, the development of molecular imaging probes targeting CAA has been attracting much attention. We previously reported the 99mTc-hydroxamamide (99mTc-Ham) complex with a bivalent benzothiazole scaffold as a binding moiety for amyloid aggregates ([99mTc]BT2) and its utility for CAA-specific imaging. However, the simultaneous generation of two radiolabeled co

Picolinic acid-based metallic chelators, e.g., neunpa and octapa, have attracted much attention as promising scaffolds for radiotheranostic agents, particularly those containing larger α-emitting radiometals. Furthermore, albumin binder (ALB) moieties, which noncovalently bind to albumin, have been utilized to improve the pharmacokinetics of radioligands targeting various biomolecules. In this study, we designed and synthesized novel neunpa and octapa derivatives (Neunpa-2 and Octapa-2, respecti

Carbonic anhydrase-IX (CA-IX) is attracting much attention as a target molecule for cancer treatment since high expression of CA-IX can lead to a poor prognosis of patients. We previously reported low-molecular-weight 111In/90Y complexes with a bivalent ureidosulfonamide scaffold ([111In/90Y]In/Y-US2) as cancer radiotheranostic agents for single photon emission computed tomography and radionuclide-based therapy targeting CA-IX. Here, we applied the US2 platform to positron emission tomography (P