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

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

doi:10.1016/j.nucmedbio.2022.02.003

Cited by 10 publications

(10 citation statements)

References 21 publications

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“…The approach of voxel-based dosimetry of companion diagnostics proposed in the present study could be used for assessing the three-dimensional distribution of the absorbed dose for α- and/or β-particle emitter-labeled therapeutics, for which estimating the radiation doses quantitatively is difficult via imaging. For example, 225 Ac-DOTATATE coupled with 68 Ga-DOTANOC in targeted α therapy of neuroendocrine tumors, 51 225 Ac-labeled hNd2 (NMT25) coupled with 89 Zr-labeled hNd2 (NMK89) for therapy of pancreatic cancer, 52 and 225 Ac-DOTA-hTAB004 coupled with 111 In-DOTA-hTAB004 for therapy of breast cancer. 53 …”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [¹⁸F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

et al. 2022

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Several radiolabeled prostate-specific membrane antigen (PSMA)-targeted agents have been developed for detecting prostate cancer, using positron emission tomography imaging and targeted radionuclide therapy. Among them, [18F]PSMA-1007 has several advantages, including a comparatively long half-life, delayed renal excretion, and compatible structure with α-/β-particle emitter-labeled therapeutics. This study aimed to characterize the preclinical pharmacokinetics and internal radiation dosimetry of [18F]PSMA-1007, as well as its repeatability and specificity for target binding using prostate tumor-bearing mice. In PSMA-positive tumor-bearing mice, the kidney showed the greatest accumulation of [18F]PSMA-1007. The distribution in the tumor attained its peak concentration of 2.8%ID/g at 112 min after intravenous injection. The absorbed doses in the tumor and salivary glands were 0.079 ± 0.010 Gy/MBq and 0.036 ± 0.006 Gy/MBq, respectively. The variance of the net influx (K i ) of [18F]PSMA-1007 to the tumor was minimal between scans performed in the same animals (within-subject coefficient of variation = 7.57%). [18F]PSMA-1007 uptake in the tumor was specifically decreased by 32% in K i after treatment with a PSMA inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA). In the present study, we investigated the in vivo preclinical characteristics of [18F]PSMA-1007. Our data from [18F]PSMA-1007 PET/computed tomography (CT) studies in a subcutaneous prostate cancer xenograft mouse model supports clinical therapeutic strategies that use paired therapeutic radiopharmaceuticals (such as [177Lu]Lu-PSMA-617), especially strategies with a quantitative radiation dose estimate for target lesions while minimizing radiation-induced toxicity to off-target tissues.

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Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [¹⁸F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

et al. 2022

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“…Based on the above-mentioned AMED/CiCLE research, NMP reported the efficacy of an 225 Ac-labeled humanized antibody for pancreatic cancer model mice with a targeting strategy of cancer-cell-related mucin MUC5AC and verified the tumor growth inhibitory effect [51].…”

Section: Current Status Of 225 Ac Distribution and Related R And D In...mentioning

confidence: 99%

Research and Development for Cyclotron Production of 225Ac from 226Ra—The Challenges in a Country Lacking Natural Resources for Medical Applications

et al. 2022

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The high therapeutic effect of targeted radioisotope/radionuclide therapy (TRT) using α-emitters, especially 225Ac, is attracting attention worldwide. However, the only 225Ac production method that has been put into practical use is extraction from a 229Th generator derived from the nuclear fuel 233U, and it is unlikely that this method alone is able to meet future global medical demand. Development towards new 225Ac production methods is in progress. These new 225Ac production methods require the irradiation of 232Th or 226Ra using an accelerator or a nuclear reactor. Global competition has already begun in the race to secure a reliable supply of 232Th and 226Ra, as well as 229Th for the conventional production method. Japan is a “resource-poor country” that depends on foreign countries for most of its needs. As such, it is difficult for Japan to secure raw materials such as 232Th and 226Ra for medical application. In this paper, we look back on our research at the National Institutes for Quantum Science and Technology (QST) in the fields of 225Ac production and 225Ac-labeled pharmaceutical development. We present the history and details of our research from 2011, as well as the development of a collaboration between QST and Nihon Medi-Physics that focuses on research into 225Ac production via 226Ra(p,2n)225Ac reaction using an accelerator. Furthermore, we review the valuable discussion at the 2018 Joint IAEA-JRC Workshop—“Supply of Actinium-225”, an international conference that we participated in. Overall, the statuses of external 225Ac supply, domestic production, and distribution are discussed, as are the latest developments in 225Ac production methods, 225Ac pharmaceuticals, and future prospects for the domestic production of 225Ac in Japan, a country lacking natural resources for medical applications.

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“…In the future, fluorescent mAbs could help guide the resection of PDAC. A humanised anti-MUC5AC antibody was labelled with 225 Actinium (Ac) for targeted radionuclide therapy and demonstrated efficacy to suppress tumour growth in mice [ 63 ]. However, none of these MUC5AC antibodies are currently in clinical trials.…”

Section: Targeting the Surfaceome Of Pancreatic Tumoursmentioning

confidence: 99%

“…Therefore, several groups used or developed anti-MUC5AC mAbs for therapy or tumour detection. When linked to 111 In [62] or 89 Zirconium (Zr) [63] radioisotopes or to a NIR dye (IRDye800CW) [64], anti-MUC5AC mAbs could preferentially target pancreatic cancer tissue compared to normal pancreatic tissue. In the future, fluorescent mAbs could help guide the resection of PDAC.…”

Section: Mucinsmentioning

confidence: 99%

Antibody-Based Approaches to Target Pancreatic Tumours

2022

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Pancreatic cancer is an aggressive cancer with a dismal prognosis. This is due to the difficulty to detect the disease at an early and curable stage. In addition, only limited treatment options are available, and they are confronted by mechanisms of resistance. Monoclonal antibody (mAb) molecules are highly specific biologics that can be directly used as a blocking agent or modified to deliver a drug payload depending on the desired outcome. They are widely used to target extracellular proteins, but they can also be employed to inhibit intracellular proteins, such as oncoproteins. While mAbs are a class of therapeutics that have been successfully employed to treat many cancers, they have shown only limited efficacy in pancreatic cancer as a monotherapy so far. In this review, we will discuss the challenges, opportunities and hopes to use mAbs for pancreatic cancer treatment, diagnostics and imagery.

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

Cited by 10 publications

References 21 publications

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [¹⁸F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [¹⁸F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

Research and Development for Cyclotron Production of 225Ac from 226Ra—The Challenges in a Country Lacking Natural Resources for Medical Applications

Antibody-Based Approaches to Target Pancreatic Tumours

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

Cited by 10 publications

References 21 publications

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [18F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [18F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

Research and Development for Cyclotron Production of 225Ac from 226Ra—The Challenges in a Country Lacking Natural Resources for Medical Applications

Antibody-Based Approaches to Target Pancreatic Tumours

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Product

Resources

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Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [¹⁸F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [¹⁸F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model