Abstract
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 derivative as an albumin binder (ALB). We performed preclinical evaluations of PSMA-DA1 as a tool for PSMA-targeting radiotheranostics using 111In, 90Y, and 225Ac. [111In]In-PSMA-DA1 demonstrated significantly greater tumor uptake and retention than a corresponding non-ALB-conjugated compound. In mice, single-photon emission computed tomography performed with [111In]In-PSMA-DA1 produced clear tumor images, and the administration of [90Y]Y-PSMA-DA1 or [225Ac]Ac-PSMA-DA1 inhibited tumor growth. [225Ac]Ac-PSMA-DA1 had antitumor effects in mice at a lower radioactivity level than [225Ac]Ac-PSMA-617, which has been reported to be clinically useful. These results indicate that PSMA-DA1 may be a useful PSMA-targeting radiotheranostic agent.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actinium / chemistry
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use*
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Cell Line, Tumor
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Cyclams / chemical synthesis
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Cyclams / metabolism
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Cyclams / pharmacokinetics
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Cyclams / therapeutic use
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Glutamate Carboxypeptidase II / metabolism*
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Humans
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Ligands
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Male
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred ICR
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Mice, SCID
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Precision Medicine / methods
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Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
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Prostatic Neoplasms, Castration-Resistant / drug therapy*
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Prostatic Neoplasms, Castration-Resistant / metabolism
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Radiopharmaceuticals / chemical synthesis
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Radiopharmaceuticals / metabolism
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Radiopharmaceuticals / pharmacokinetics
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Radiopharmaceuticals / therapeutic use*
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Single Photon Emission Computed Tomography Computed Tomography
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Urea / analogs & derivatives
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Urea / metabolism
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Urea / pharmacokinetics
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Urea / therapeutic use
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Xenograft Model Antitumor Assays
Substances
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Actinium-225
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Antineoplastic Agents
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Cyclams
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Ligands
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Membrane Glycoproteins
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Radiopharmaceuticals
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Urea
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Glutamate Carboxypeptidase II
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PSMA protein, mouse
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Actinium