ImmunoPET using engineered antibody fragments: fluorine-18 labeled diabodies for same-day imaging

• Published in: Tumor biology Vol. 33; no. 3; pp. 669 - 677
• Main Authors: Olafsen, Tove, Sirk, Shannon J., Olma, Sebastian, Shen, Clifton K.-F., Wu, Anna M.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-06-2012; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Breast Neoplasms - diagnostic imaging; Cancer Research; Cell Line, Tumor; Female; Fluorine Radioisotopes - chemistry; Humans; Immunoconjugates - chemistry; Immunoconjugates - immunology; Isotopes; Labeling; Mice; Mice, Nude; Molecular Imaging; Multimodal Imaging; Positron-Emission Tomography; Receptor, ErbB-2 - immunology; Research Article; Rodents; Single-Chain Antibodies - chemistry; Single-Chain Antibodies - immunology; Tomography; Tomography, X-Ray Computed; Transplantation, Heterologous; Tumors; Small animal imaging; Antibody fragment; Positron emission tomography; Radiochemistry; HER2 imaging
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-012-0365-8

Combining the specificity of tumor-targeting antibodies with the sensitivity and quantification offered by positron emission tomography (PET) provides tremendous opportunities for molecular characterization of tumors in vivo. Until recently, significant challenges have been faced when attempting to combine antibodies which show long biological half-lives and positron-emitting radionuclides with comparably short physical half-lives, in particular
18
F (half-life, 109 min). A fast and simple microwave-assisted method of generating
N
-succinimidyl-4-[
18
F]fluorobenzoate has been developed and employed for radiolabeling a small, rapidly targeting HER2-specific engineered antibody fragment, the cys-diabody. Using this tracer, HER2-positive tumor xenografts in mice were detected at 1–4 h post-injection by microPET. This confirms the rapid kinetics of [
18
F]fluorobenzoyl cys-diabody localization, and demonstrates the feasibility of same-day immunoPET imaging. This approach can be broadly applied to antibodies targeting cell surface biomarkers for molecular imaging of tumors and should be highly translatable for clinical use.