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.
Highlights
The overexpression of the folate receptor (FR) on various cancer types makes it an attractive target for diagnostic radiopharmaceuticals
HPLC analyses of the radiofolates showed an increase in retention time from 2.2 min for free [55Co]CoCl2 to 11.3 min for [55Co]Co-cm10 (Figure 2A) and 10.7 min for [55Co]Co-rf42 (Figure 2B)
The retention times of the radiofolates closely matched the in retention time from 2.2 min for free [55 Co]CoCl2 to 11.3 min for [55 Co]Co-cm10 (Figure 2A) and 10.7 retention times of 10.9 min and 10.5 min of the non-radiolabeled precursors cm10 (Figure 2C) and min for [55 Co]Co-rf42 (Figure 2B)
Summary
The overexpression of the folate receptor (FR) on various cancer types makes it an attractive target for diagnostic radiopharmaceuticals. Only two FR-imaging agents have been used in clinical trials, [99m Tc]Tc-EC20 and [111 In]In-DTPA-folate, and only [99m Tc]Tc-EC20 is currently used in investigational studies under the trade name [99m Tc]Tc-Etarfolatide (Endocyte Inc., West Lafayette, IN, USA) [4,5]. In addition to a bifunctional chelator, each bioconjugate consists of a folic acid molecule consists of a folicand acida molecule for FR-targeting and a p-iodophenyl-based albumin-binding entity. It has has been been shown shown that that the profile of of aa small small molecule molecule can can be be altered by making making small chelator, complexed metal). Is not subject is to not in vivo reduction and transchelation metalloproteins interesting advantages it offers
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