This is a first in human study that will assess the safety and diagnostic performance of [18F]RP-115 (fluorine-18 labeled RP115), a positron emission tomography (PET) agent. This agent has the potential to identify the early changes that occur in the brains of patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD).

开始日期2021-11-02

申办/合作机构

The University of California, San Francisco

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100 项与 RP-115 相关的临床结果

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100 项与 RP-115 相关的转化医学

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100 项与 RP-115 相关的专利（医药）

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项与 RP-115 相关的文献（医药）

2025-03-01·Nuclear Medicine and Biology

First-in-human healthy volunteer dosimetry studies of the excitatory amino acid transporter 2 (EAAT2) PET imaging tracer methyl N4-(7-[18F]fluoro-9H-fluoren-2-yl)asparaginate, [18F]RP-115

Article

作者: Chao, Chih-Kai ; Blecha, Joseph ; Polvoy, Ilona ; Gerdes, John M ; Nillo, Ryan Michael ; Seo, Youngho ; Forsayeth, John R ; VanBrocklin, Henry F ; Wilson, David M

OBJECTIVE AND BACKGROUNDThe objective of this first-in-human study was to investigate the radiosynthesis, and the preliminary safety, biodistribution, and organ radiation dosimetry of the positron emission tomography (PET) imaging tracer methyl N⁴-([¹⁸F]7-fluoro-9H-fluoren-2-yl)asparaginate, known as [¹⁸F]RP-115, in a small cohort (n=8) of healthy volunteers. The [¹⁸F]RP-115 tracer is a methyl ester prodrug and undergoes metabolic saponification in the central nervous system to generate the corresponding carboxylic acid form that selectively binds to the excitatory amino acid transporter 2 (EAAT2) protein.PROCEDURES AND METHODSA multi-step high molar activity tracer radiosynthesis was devised to produce doses. Eight healthy human participants (four male and four female), aged 56-75, received a bolus intravenous injection of [¹⁸F]RP-115 (administered activity range: 70.3-355 MBq) prior to a total of 94 min of PET-MR scanning performed as three sequential scanning sessions. Regional tissue volumes of interest were defined, time-integrated activity coefficients (TIAC) were derived, and then estimates of organ and tissue activities and effective doses (whole body) were calculated, with two versions of OLINDA software (1.1 and 2.0) that incorporated two tissue weighting factor sets (ICRP-60 and -103), respectively.MAIN FINDINGSTracer was routinely produced in good radiochemical yields and as suitable high molar activity doses for injection. The [¹⁸F]RP-115 injections and PET-MR scans were well-tolerated and no adverse events were reported (≤48 h). Radioactivity was widely biodistributed with good organ uptake. TIACs and estimated radiation organ doses were determined, for which a few statistically significant estimated organ dose differences between males and females were noted. The kidneys were identified as the critical target organ.PRINCIPAL CONCLUSIONSInjection of [¹⁸F]RP-115 was considered safe. The estimated kidney radiation doses relative to administered radioactivity identified a more optimal human [¹⁸F]RP-115 tracer injected amount of <211 MBq. This more optimal [¹⁸F]RP-115 tracer injected activity definition is similar to the amounts used for other established [¹⁸F]labeled clinical PET tracers such as [¹⁸F]FDG, and it will be used in future RP-115 clinical PET imaging studies.

100 项与 RP-115 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床2期	美国	The University of California, San Francisco	2021-11-02
额颞痴呆	临床2期	美国	The University of California, San Francisco	2021-11-02