New ⁵⁵Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging

• Main Authors: Lauren L. Radford, Solana Fernandez, Rebecca Beacham, Retta El Sayed, Renata Farkas, Martina Benešová, Cristina Müller, Suzanne E. Lapi
• Format: Article
• Language: English
• Published: MDPI AG 2019-11-01
• Series: Pharmaceuticals
• Subjects: folic acid; folate receptors; cobalt-55; pet imaging; albumin binder; ovarian cancer
• Online Access: https://www.mdpi.com/1424-8247/12/4/166

Overexpression of folate receptors (FRs) on different tumor types (e.g., ovarian, lung) make FRs attractive in vivo targets for directed diagnostic/therapeutic agents. Currently, no diagnostic agent suitable for positron emission tomography (PET) has been adopted for clinical FR imaging. In this work, two ⁵⁵Co-labeled albumin-binding folate derivatives-[⁵⁵Co]Co-cm10 and [⁵⁵Co]Co-rf42-with characteristics suitable for PET imaging have been developed and evaluated. High radiochemical yields (≥95%) and in vitro stabilities (≥93%) were achieved for both compounds, and cell assays demonstrated FR-mediated uptake. Both ⁵⁵Co-labeled folate conjugates demonstrated high tumor uptake of 17% injected activity per gram of tissue (IA/g) at 4 h in biodistribution studies performed in KB tumor-bearing mice. Renal uptake was similar to other albumin-binding folate derivatives, and liver uptake was lower than that of previously reported [⁶⁴Cu]Cu-rf42. Small animal PET/CT images confirmed the biodistribution results and showed the clear delineation of FR-expressing tumors.