A Phase I Trial to Assess Safety, Tolerability, Pharmacokinetics, Radiation Dosimetry, and Positron Emission Tomography (PET) Imaging Properties of 89Zr-labeled hNd2 (NMK89) in Patients With Pancreatic Cancer Histologically Positive for MUC5AC

This trial will be a non-randomized, Phase I trial to evaluate safety, tolerability, biodistribution, radiation dosimetry, pharmacokinetics and PET imaging properties following an infusion of 37 MBq (1 mCi) of 89Zr-labeled hNd2* (NMK89) in patients with pancreatic cancer that are positive for MUC5AC. Image acquisition is conducted using a PET/CT machine.
* hNd2: Recombinant humanized Nd2 (anti-human MUC5AC monoclonal antibody)

开始日期2023-10-31

申办/合作机构

Nihon Medi-Physics Co., Ltd.

100 项与抗muc5ac RDC(住友制药) 相关的临床结果

登录后查看更多信息

100 项与抗muc5ac RDC(住友制药) 相关的转化医学

登录后查看更多信息

100 项与抗muc5ac RDC(住友制药) 相关的专利（医药）

登录后查看更多信息

项与抗muc5ac RDC(住友制药) 相关的文献（医药）

2022-05-01·Nuclear Medicine and Biology4区 · 医学

Radiation dosimetry and efficacy of an 89Zr/225Ac-labeled humanized anti-MUC5AC antibody

4区 · 医学

Article

作者: Tanaka, Akihiro ; Okumura, Yuki ; Matono, Mitsuhiro ; Hayashi, Akio ; Sato, Mikiko ; Otsuki, Kumiko ; Kobashi, Nobuya ; Nakata, Norihito

INTRODUCTIONTheranostic applications are currently difficult to achieve owing to the limited evaluation of suitable chelators for therapeutic nuclides, such as ²²⁵Ac and ²²⁷Th. With a focus on targeted α therapy and theranostics using human IgG as a drug-delivery system (i.e., combining highly cytotoxic α-particle emitter radiation with efficient tumor targeting), we developed a recombinant humanized Nd2 (hNd2) as an anti-MUC5AC antibody since MUC5AC is highly expressed in patients with pancreatic cancer. Therefore, we aimed to evaluate the performance of ⁸⁹Zr- (for diagnosis) and ²²⁵Ac- (for therapy) labeling of these antibodies using well-controlled radioisotope (RI)-labeling technology in pancreatic cancer mouse models.METHODS⁸⁹Zr-labeled hNd2 (NMK89) and ²²⁵Ac-labeled hNd2 (NMT25) were manufactured by chemical conjugation using affinity peptides. A binding assay and the evaluation of plasma stability were performed in vitro to confirm the properties of NMK89 and NMT25. In vivo, we evaluated biodistribution, positron emission tomography (PET)/computed tomography (CT) imaging, antitumor effects, and toxicity. Moreover, the exposure dose in humans was estimated based on the biodistribution evaluation in normal mice.RESULTSNMK89 and NMT25 showed binding specificity to MUC5AC and stability with radiochemical purity ≥90% in mice and human plasma following incubation for 168 h. NMK89 showed high accumulation in tumors and low non-specific accumulation in normal tissues. The antitumor effect of NMT25 was dose-dependent and significantly suppressed tumor growth in the NMT25 treatment groups compared with the control group (p < 0.05). NMK89 and NMT25 showed similar pharmacokinetics and biodistribution characteristics. Additionally, the human estimated exposure dose of NMK89 and NMT25 was confirmed, and the effective dose of NMK89 and NMT25 was 0.33 mSv/MBq and 177.5 mSv/MBq, respectively.CONCLUSIONNMK89 showed specific accumulation in the MUC5AC-expressing tumors, while NMT25 showed strong antitumor effects. These results suggest NMK89 and NMT25 as promising theranostic agents for pancreatic cancer.

100 项与抗muc5ac RDC(住友制药) 相关的药物交易

登录后查看更多信息