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

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 wor...

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Autores principales: Radford, Lauren L., Fernandez, Solana, Beacham, Rebecca, El Sayed, Retta, Farkas, Renata, Benešová, Martina, Müller, Cristina, Lapi, Suzanne E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958329/
https://www.ncbi.nlm.nih.gov/pubmed/31717279
http://dx.doi.org/10.3390/ph12040166
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author Radford, Lauren L.
Fernandez, Solana
Beacham, Rebecca
El Sayed, Retta
Farkas, Renata
Benešová, Martina
Müller, Cristina
Lapi, Suzanne E.
author_facet Radford, Lauren L.
Fernandez, Solana
Beacham, Rebecca
El Sayed, Retta
Farkas, Renata
Benešová, Martina
Müller, Cristina
Lapi, Suzanne E.
author_sort Radford, Lauren L.
collection PubMed
description 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 (55)Co-labeled albumin-binding folate derivatives-[(55)Co]Co-cm10 and [(55)Co]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 (55)Co-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 [(64)Cu]Cu-rf42. Small animal PET/CT images confirmed the biodistribution results and showed the clear delineation of FR-expressing tumors.
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spelling pubmed-69583292020-01-23 New (55)Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging Radford, Lauren L. Fernandez, Solana Beacham, Rebecca El Sayed, Retta Farkas, Renata Benešová, Martina Müller, Cristina Lapi, Suzanne E. Pharmaceuticals (Basel) Article 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 (55)Co-labeled albumin-binding folate derivatives-[(55)Co]Co-cm10 and [(55)Co]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 (55)Co-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 [(64)Cu]Cu-rf42. Small animal PET/CT images confirmed the biodistribution results and showed the clear delineation of FR-expressing tumors. MDPI 2019-11-08 /pmc/articles/PMC6958329/ /pubmed/31717279 http://dx.doi.org/10.3390/ph12040166 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Radford, Lauren L.
Fernandez, Solana
Beacham, Rebecca
El Sayed, Retta
Farkas, Renata
Benešová, Martina
Müller, Cristina
Lapi, Suzanne E.
New (55)Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging
title New (55)Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging
title_full New (55)Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging
title_fullStr New (55)Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging
title_full_unstemmed New (55)Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging
title_short New (55)Co-labeled Albumin-Binding Folate Derivatives as Potential PET Agents for Folate Receptor Imaging
title_sort new (55)co-labeled albumin-binding folate derivatives as potential pet agents for folate receptor imaging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958329/
https://www.ncbi.nlm.nih.gov/pubmed/31717279
http://dx.doi.org/10.3390/ph12040166
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