The value of 18F-FDG PET/CT imaging in breast cancer staging.

Journal and index pages often block iframe embedding. This reader keeps the evidence details in Orthonotes and leaves the source page one click away.

Abstract

[Indexed for MEDLINE] 20. Nucl Med Biol. 2025 May-Jun;144-145:109001. doi: 10.1016/j.nucmedbio.2025.109001. Epub 2025 Feb 14. Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques. Sasaki T(1), Kimura S(2), Noda A(2), Murakami Y(2), Miyoshi S(2), Akehi M(3), Ochiai K(4), Watanabe M(5), Higuchi T(6), Matsuura E(5). Author information: (1)Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan. Electronic address: t-sasaki@cc.okayama-u.ac.jp. (2)Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. (3)Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan; Neutron Therapy Research Center, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan. (4)School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino-shi, Tokyo 180-8602, Japan. (5)Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan. (6)Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan; Department of Nuclear Medicine and Comprehensive Heart Failure Center, University Hospital of Würzburg, Oberdürrbacher Strasse 6, 97080 Würzburg, Germany. BACKGROUND: Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of 89Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies. METHODS: Selected IgG was conjugated to desferrioxamine (DFO), labelled with 89Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, 89Zr-labelled Fab, as well as that of [89Zr]Zr-DFO and [89Zr]Zr-oxalate, the expected metabolites of 89Zr- labelled IgG, was also assessed. RESULTS: After 89Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the 89Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the 89Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in 89Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [89Zr]Zr-DFO was rapidly excreted into the urine, whereas [89Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body. CONCLUSION: In the non-human primate cynomolgus macaque, 89Zr- labelled IgG accumulated in the kidneys and the liver. However, [89Zr]Zr-DFO and 89Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of 89Zr- labelled IgG. Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.nucmedbio.2025.109001