Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules

Pyry Dillemuth; Abiodun Ayo; Xiaoqing Zhuang; Petter Lövdahl; Heidi Liljenbaeck; Salli Kaernae; Tatsiana Auchynnikava; Jonne Kunnas; Jesse Ponkamo; Maxwell W. G. Miner; Johan Rajander; Jessica M. Rosenholm; Anne Roivainen; Anu J. Airaksinen; Pirjo Laakkonen; Xiang-Guo Li

doi:10.1186/s41181-025-00368-1

Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules

Pyry Dillemuth
, Abiodun Ayo
, Xiaoqing Zhuang
, Petter Lövdahl
, Heidi Liljenbaeck
, Salli Kaernae
, Tatsiana Auchynnikava
, Jonne Kunnas
, Jesse Ponkamo
, Maxwell W. G. Miner
, Johan Rajander
, Jessica M. Rosenholm
, Anne Roivainen
, Anu J. Airaksinen
, Pirjo Laakkonen
, Xiang-Guo Li

Research output: Contribution to journal › Article › Scientific › peer-review

2 Citations (Scopus)

8 Downloads (Pure)

Abstract

Background: Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[ ¹⁸F]fluoronicotinic acid ([ ¹⁸F]FNA) have been prepared and successfully employed for ¹⁸F-labeling of diverse biomolecules, including peptides. The utility of [ ¹⁸F]FNA as a prosthetic compound has been demonstrated in both preclinical and clinical settings, including radiopharmaceuticals targeting prostate-specific membrane antigen and poly(ADP ribose) polymerase inhibitors. This study aims to evaluate a [ ¹⁸F]FNA-conjugated nonapeptide, [ ¹⁸F]FNA-N-CooP, for positron emission tomography imaging of intracranial BT12 glioblastoma xenografts in a mouse model. Additionally, this study highlights the importance of including control experiments with prosthetic compound alone when it constitutes a major radiometabolite. Results: [ ¹⁸F]FNA-N-CooP successfully delineated intracranial glioblastoma xenografts yielding a standardized uptake value of 0.21 ± 0.03 (n = 4) and a tumor-to-brain ratio of 1.84 ± 0.29. Ex vivo autoradiography of tumor tissue showed a partial co-localization between radioactivity uptake and the target fatty acid binding protein 3 expression. However, in vivo instability of [ ¹⁸F]FNA-N-CooP was observed, with [ ¹⁸F]FNA identified as a major radiometabolite. Notably, control studies using [ ¹⁸F]FNA alone also visualized tumors, producing a standardized uptake value of 0.90 ± 0.10 (n = 4) and a tumor-to-brain ratio of 1.51 ± 0.08. Conclusions: Both [ ¹⁸F]FNA-N-CooP and [ ¹⁸F]FNA enabled PET visualization of human glioblastoma in the mouse model. However, the prominent presence of [ ¹⁸F]FNA as radiometabolite complicates the interpretation of [ ¹⁸F]FNA-N-CooP PET data, suggesting that the observed radioactivity uptake may primarily originate from [ ¹⁸F]FNA and other radiometabolites. Enhancing peptide stability is essential for improving imaging specificity. This study underscores the critical need to assess the imaging contributions of prosthetic groups when they function as significant radiometabolites.

Original language	English
Article number	40
Number of pages	15
Journal	EJNMMI Radiopharmacy and Chemistry
Volume	10
Issue number	1
DOIs	https://doi.org/10.1186/s41181-025-00368-1
Publication status	Published - 8 Jul 2025
MoE publication type	A1 Journal article-refereed

Funding

We thank the research grants from the Finnish Cancer Foundation, the Finnish Cultural Foundation, the Turku University Foundation, Turku University Hospital, Sigrid Jusélius Foundation, and the Research Council of Finland (decision numbers 368560, 350117). This research was partially supported by the Research Council of Finland’s Flagship InFLAMES and ImmunoCAP projects, and the funding Decision Numbers were 337530, 357910, 352727.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

6-[F-18]fluoronicotinic acid
Fluorine-18
Pet
Peptide radiolabeling
Prosthetic group

Access to Document

10.1186/s41181-025-00368-1Licence: CC BY-NC-ND

s41181-025-00368-1Final published version, 2.19 MBLicence: CC BY-NC-ND

https://urn.fi/URN:NBN:fi-fe2025091195332

Cite this

Dillemuth, P., Ayo, A., Zhuang, X., Lövdahl, P., Liljenbaeck, H., Kaernae, S., Auchynnikava, T., Kunnas, J., Ponkamo, J., Miner, M. W. G., Rajander, J., Rosenholm, J. M., Roivainen, A., Airaksinen, A. J., Laakkonen, P., & Li, X.-G. (2025). Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules. EJNMMI Radiopharmacy and Chemistry, 10(1), Article 40. https://doi.org/10.1186/s41181-025-00368-1

@article{64250d13745e4fa3a4c2f63548d3d30c,

title = "Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules",

abstract = "Background: Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[ 18F]fluoronicotinic acid ([ 18F]FNA) have been prepared and successfully employed for 18F-labeling of diverse biomolecules, including peptides. The utility of [ 18F]FNA as a prosthetic compound has been demonstrated in both preclinical and clinical settings, including radiopharmaceuticals targeting prostate-specific membrane antigen and poly(ADP ribose) polymerase inhibitors. This study aims to evaluate a [ 18F]FNA-conjugated nonapeptide, [ 18F]FNA-N-CooP, for positron emission tomography imaging of intracranial BT12 glioblastoma xenografts in a mouse model. Additionally, this study highlights the importance of including control experiments with prosthetic compound alone when it constitutes a major radiometabolite. Results: [ 18F]FNA-N-CooP successfully delineated intracranial glioblastoma xenografts yielding a standardized uptake value of 0.21 ± 0.03 (n = 4) and a tumor-to-brain ratio of 1.84 ± 0.29. Ex vivo autoradiography of tumor tissue showed a partial co-localization between radioactivity uptake and the target fatty acid binding protein 3 expression. However, in vivo instability of [ 18F]FNA-N-CooP was observed, with [ 18F]FNA identified as a major radiometabolite. Notably, control studies using [ 18F]FNA alone also visualized tumors, producing a standardized uptake value of 0.90 ± 0.10 (n = 4) and a tumor-to-brain ratio of 1.51 ± 0.08. Conclusions: Both [ 18F]FNA-N-CooP and [ 18F]FNA enabled PET visualization of human glioblastoma in the mouse model. However, the prominent presence of [ 18F]FNA as radiometabolite complicates the interpretation of [ 18F]FNA-N-CooP PET data, suggesting that the observed radioactivity uptake may primarily originate from [ 18F]FNA and other radiometabolites. Enhancing peptide stability is essential for improving imaging specificity. This study underscores the critical need to assess the imaging contributions of prosthetic groups when they function as significant radiometabolites.",

keywords = "6-[F-18]fluoronicotinic acid, Fluorine-18, Pet, Peptide radiolabeling, Prosthetic group",

author = "Pyry Dillemuth and Abiodun Ayo and Xiaoqing Zhuang and Petter L{\"o}vdahl and Heidi Liljenbaeck and Salli Kaernae and Tatsiana Auchynnikava and Jonne Kunnas and Jesse Ponkamo and Miner, \{Maxwell W. G.\} and Johan Rajander and Rosenholm, \{Jessica M.\} and Anne Roivainen and Airaksinen, \{Anu J.\} and Pirjo Laakkonen and Xiang-Guo Li",

year = "2025",

month = jul,

day = "8",

doi = "10.1186/s41181-025-00368-1",

language = "English",

volume = "10",

journal = "EJNMMI Radiopharmacy and Chemistry",

issn = "2365-421X",

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Dillemuth, P, Ayo, A, Zhuang, X, Lövdahl, P, Liljenbaeck, H, Kaernae, S, Auchynnikava, T, Kunnas, J, Ponkamo, J, Miner, MWG, Rajander, J , Rosenholm, JM, Roivainen, A, Airaksinen, AJ, Laakkonen, P & Li, X-G 2025, 'Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules', EJNMMI Radiopharmacy and Chemistry, vol. 10, no. 1, 40. https://doi.org/10.1186/s41181-025-00368-1

Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules. / Dillemuth, Pyry; Ayo, Abiodun; Zhuang, Xiaoqing et al.
In: EJNMMI Radiopharmacy and Chemistry, Vol. 10, No. 1, 40, 08.07.2025.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake

T2 - implications for radiolabeling design of biomolecules

AU - Dillemuth, Pyry

AU - Ayo, Abiodun

AU - Zhuang, Xiaoqing

AU - Lövdahl, Petter

AU - Liljenbaeck, Heidi

AU - Kaernae, Salli

AU - Auchynnikava, Tatsiana

AU - Kunnas, Jonne

AU - Ponkamo, Jesse

AU - Miner, Maxwell W. G.

AU - Rajander, Johan

AU - Rosenholm, Jessica M.

AU - Roivainen, Anne

AU - Airaksinen, Anu J.

AU - Laakkonen, Pirjo

AU - Li, Xiang-Guo

PY - 2025/7/8

Y1 - 2025/7/8

N2 - Background: Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[ 18F]fluoronicotinic acid ([ 18F]FNA) have been prepared and successfully employed for 18F-labeling of diverse biomolecules, including peptides. The utility of [ 18F]FNA as a prosthetic compound has been demonstrated in both preclinical and clinical settings, including radiopharmaceuticals targeting prostate-specific membrane antigen and poly(ADP ribose) polymerase inhibitors. This study aims to evaluate a [ 18F]FNA-conjugated nonapeptide, [ 18F]FNA-N-CooP, for positron emission tomography imaging of intracranial BT12 glioblastoma xenografts in a mouse model. Additionally, this study highlights the importance of including control experiments with prosthetic compound alone when it constitutes a major radiometabolite. Results: [ 18F]FNA-N-CooP successfully delineated intracranial glioblastoma xenografts yielding a standardized uptake value of 0.21 ± 0.03 (n = 4) and a tumor-to-brain ratio of 1.84 ± 0.29. Ex vivo autoradiography of tumor tissue showed a partial co-localization between radioactivity uptake and the target fatty acid binding protein 3 expression. However, in vivo instability of [ 18F]FNA-N-CooP was observed, with [ 18F]FNA identified as a major radiometabolite. Notably, control studies using [ 18F]FNA alone also visualized tumors, producing a standardized uptake value of 0.90 ± 0.10 (n = 4) and a tumor-to-brain ratio of 1.51 ± 0.08. Conclusions: Both [ 18F]FNA-N-CooP and [ 18F]FNA enabled PET visualization of human glioblastoma in the mouse model. However, the prominent presence of [ 18F]FNA as radiometabolite complicates the interpretation of [ 18F]FNA-N-CooP PET data, suggesting that the observed radioactivity uptake may primarily originate from [ 18F]FNA and other radiometabolites. Enhancing peptide stability is essential for improving imaging specificity. This study underscores the critical need to assess the imaging contributions of prosthetic groups when they function as significant radiometabolites.

AB - Background: Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[ 18F]fluoronicotinic acid ([ 18F]FNA) have been prepared and successfully employed for 18F-labeling of diverse biomolecules, including peptides. The utility of [ 18F]FNA as a prosthetic compound has been demonstrated in both preclinical and clinical settings, including radiopharmaceuticals targeting prostate-specific membrane antigen and poly(ADP ribose) polymerase inhibitors. This study aims to evaluate a [ 18F]FNA-conjugated nonapeptide, [ 18F]FNA-N-CooP, for positron emission tomography imaging of intracranial BT12 glioblastoma xenografts in a mouse model. Additionally, this study highlights the importance of including control experiments with prosthetic compound alone when it constitutes a major radiometabolite. Results: [ 18F]FNA-N-CooP successfully delineated intracranial glioblastoma xenografts yielding a standardized uptake value of 0.21 ± 0.03 (n = 4) and a tumor-to-brain ratio of 1.84 ± 0.29. Ex vivo autoradiography of tumor tissue showed a partial co-localization between radioactivity uptake and the target fatty acid binding protein 3 expression. However, in vivo instability of [ 18F]FNA-N-CooP was observed, with [ 18F]FNA identified as a major radiometabolite. Notably, control studies using [ 18F]FNA alone also visualized tumors, producing a standardized uptake value of 0.90 ± 0.10 (n = 4) and a tumor-to-brain ratio of 1.51 ± 0.08. Conclusions: Both [ 18F]FNA-N-CooP and [ 18F]FNA enabled PET visualization of human glioblastoma in the mouse model. However, the prominent presence of [ 18F]FNA as radiometabolite complicates the interpretation of [ 18F]FNA-N-CooP PET data, suggesting that the observed radioactivity uptake may primarily originate from [ 18F]FNA and other radiometabolites. Enhancing peptide stability is essential for improving imaging specificity. This study underscores the critical need to assess the imaging contributions of prosthetic groups when they function as significant radiometabolites.

KW - 6-[F-18]fluoronicotinic acid

KW - Fluorine-18

KW - Pet

KW - Peptide radiolabeling

KW - Prosthetic group

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Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules

Abstract

Funding

UN SDGs

Keywords

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NanoPET: Early detection of breast cancer lung metastasis with high precision using new nanoparticle-based PET imaging agents

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Rapid cleavage of 6-[18F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules

Abstract

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Projects

NanoPET: Early detection of breast cancer lung metastasis with high precision using new nanoparticle-based PET imaging agents

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