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

Abstract

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.

Development of Folate Receptor−Targeted PET Radiopharmaceuticals for Tumor Imaging—A Bench-to-Bedside Journey

“…In contrast, the 55 Co-labeled folate conjugate (14, Figure 4) exhibited lower liver uptake compared to the 64 Cu-labeled radiolabeled folates. This observation was explained by the fact that 55 Co in contrast to 64 Cu does not accumulate in the liver when it is released by the DOTA or NODAGA chelator since it behaves as a calcium mimetic [49].…”

“…In vitro cell binding studies showed specificity of the folate derivative to FR, however, no results of in vivo studies with FR-positive tumor-bearing mice have been reported. In 2019, Radford et al [ 49 ] reported the radiolabeling of folate conjugates rf42 and cm10 with 55 Co for PET imaging representing the first cobalt-55-labeled radiolabeled folates ever to be reported in the literature. A high radiochemical yield of ≥95% and in vitro stability of ≥93% of both tracers were obtained.…”

Radiosynthesis and Preclinical Evaluation of [68Ga]Ga-NOTA-Folate for PET Imaging of Folate Receptor β Positive Macrophages

“…The beta isoform of the folate receptor (FR-β), distinctly expressed on activated macrophages, has been recognized as a promising imaging marker for inflammatory conditions such as rheumatoid arthritis 2 7,8 , with the latter two already reaching initial clinical phase 9,10 . Other recently developed FR-targeted tracers include reduced 18 F-folate conjugates 11 , 55 Co-labeled albumin-binding folate derivatives 12 and [ 68 Ga]NOTA-folate 13 , which have been investigated for imaging FR-overexpressing tumors in preclinical studies. In a previous study, we showed that 18 F-FOL PET successfully visualized FR-β-positive macrophages in mouse and rabbit models of atherosclerosis 3 .…”

Pharmacokinetic Properties of 68Ga-labelled Folic Acid Conjugates: Improvement Using HEHE Tag

“…In the ongoing clinical trial the first 68 Ga-folate PET radiotracer ([ 68 Ga]Ga-EC2115) is tested to evaluate the possibility of differentiating COPD (chronic obstructive pulmonary disease) patients from control subjects and determine whether PET signal correlates with measurements of inflammation, disease severity, and rate of disease progression [16]. Currently, data on several folic acid based radiopharmaceuticals with PET-radionuclides, such as 18 F, 68/66 Ga, 152 Tb, 64 Cu, 55 Co and 44 Sc have been presented and even more new conjugates are under development [17][18][19][20][21][22][23].…”