A short PEG linker alters the in vivo pharmacokinetics of trastuzumab to yield high-contrast immuno-PET images

• Published in: Journal of Materials Chemistry B Vol. 9; no. 13; pp. 2993 - 2997
• Main Authors: Lee, Woonghee, Bobba, Kondapa Naidu, Kim, Jung Young, Park, Hyun, Bhise, Abhinav, Kim, Wanook, Lee, Kiwoong, Rajkumar, Subramani, Nam, Bora, Lee, Kyo Chul, Lee, Sang Hyuk, Ko, Sanghwan, Lee, Hye Jin, Jung, Sang Taek, Yoo, Jeongsoo
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry (RSC) 07.04.2021; Royal Society of Chemistry
• Subjects: Antibodies; Antineoplastic Agents, Immunological; blood; Blood circulation; Breast cancer; Breast Neoplasms; breasts; chemical bonding; Female; Humans; Image contrast; Pharmacokinetics; Polyethylene Glycols; Positron emission; Positron emission tomography; Radiation effects; radiolabeling; Radiopharmaceuticals; Retention time; Tomography; Trastuzumab; Tumors
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d0tb02911d

The prolonged blood circulation of the radiolabeled antibody conjugates is problematic when using immuno-PET imaging due to the increased radiation exposure and longer hospitalization required until sufficient contrast develops. In contrast to the prevailing belief that PEGylation prolongs blood retention time, we observed that a PEGylated antibody with a short PEG 8 linker cleared much faster from the blood while maintaining tumor uptake compared to its non-PEGylated counterpart. Breast tumors were clearly visualized with a very high tumor-to-background ratio as early as 24 h after injection in immuno-positron emission tomography (PET) imaging.