64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats

Mikkola Kirsi; Cheng-Bin Yim; Fagerholm Veronica; Ishizu Tamiko; Viki-Veikko Elomaa; Johan Rajander; Jurttila Jori; Saanijoki Tiina; Tolvanen Tuula; Tirri Marko; Gourni Eleni; Béhé Martin; Gotthardt Martin; Reubi Jean Claude; Mäcke Helmut; Roivainen Anne; Olof Solin; Nuutila Pirjo

doi:10.1007/s11307-013-0691-2

64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats

Mikkola Kirsi, Cheng-Bin Yim, Fagerholm Veronica, Ishizu Tamiko, Viki-Veikko Elomaa, Johan Rajander, Jurttila Jori, Saanijoki Tiina, Tolvanen Tuula, Tirri Marko, Gourni Eleni, Béhé Martin, Gotthardt Martin, Reubi Jean Claude, Mäcke Helmut, Roivainen Anne, Olof Solin, Nuutila Pirjo

Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review

60 Citeringar (Scopus)

Sammanfattning

Purpose

Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle14,Lys40(Ahx-NODAGA-64Cu)NH2]-exendin-4 ([64Cu]NODAGA-exendin-4) and [Nle14,Lys40(Ahx-NODAGA-68Ga)NH2]-exendin-4 ([68Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents.

Procedures

The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated.

Results

We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [64Cu]NODAGA-exendin-4 and [68Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively.

Conclusion

[64Cu]NODAGA-exendin-4 might be more effective for labelling islets than [68Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [68Ga]NODAGA-exendin-4 compared to [64Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [64Cu]NODAGA-exendin-4 as a clinical tracer.

Originalspråk	Odefinierat/okänt
Sidor (från-till)	255–263
Tidskrift	Molecular Imaging and Biology
Volym	16
Nummer	2
DOI	https://doi.org/10.1007/s11307-013-0691-2
Status	Publicerad - 2014
MoE-publikationstyp	A1 Tidskriftsartikel-refererad

Åtkomst av dokument

10.1007/s11307-013-0691-2

http://link.springer.com/article/10.1007/s11307-013-0691-2/fulltext.html

Citera det här

Kirsi, M., Yim, C.-B., Veronica, F., Tamiko, I., Elomaa, V.-V., Rajander, J., Jori, J., Tiina, S., Tuula, T., Marko, T., Eleni, G., Martin, B., Martin, G., Jean Claude, R., Helmut, M., Anne, R., Solin, O., & Pirjo, N. (2014). 64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats. Molecular Imaging and Biology, 16(2), 255–263. https://doi.org/10.1007/s11307-013-0691-2

@article{37c67d3ea8e44675960d51e5132cf6cb,

title = "64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats",

abstract = "Purpose Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle14,Lys40(Ahx-NODAGA-64Cu)NH2]-exendin-4 ([64Cu]NODAGA-exendin-4) and [Nle14,Lys40(Ahx-NODAGA-68Ga)NH2]-exendin-4 ([68Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents. Procedures The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated. Results We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [64Cu]NODAGA-exendin-4 and [68Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively. Conclusion [64Cu]NODAGA-exendin-4 might be more effective for labelling islets than [68Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [68Ga]NODAGA-exendin-4 compared to [64Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [64Cu]NODAGA-exendin-4 as a clinical tracer.",

author = "Mikkola Kirsi and Cheng-Bin Yim and Fagerholm Veronica and Ishizu Tamiko and Viki-Veikko Elomaa and Johan Rajander and Jurttila Jori and Saanijoki Tiina and Tolvanen Tuula and Tirri Marko and Gourni Eleni and B{\'e}h{\'e} Martin and Gotthardt Martin and {Jean Claude}, Reubi and M{\"a}cke Helmut and Roivainen Anne and Olof Solin and Nuutila Pirjo",

year = "2014",

doi = "10.1007/s11307-013-0691-2",

language = "Odefinierat/ok{\"a}nt",

volume = "16",

pages = "255–263",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer",

number = "2",

}

Kirsi, M, Yim, C-B, Veronica, F, Tamiko, I, Elomaa, V-V, Rajander, J, Jori, J, Tiina, S, Tuula, T, Marko, T, Eleni, G, Martin, B, Martin, G, Jean Claude, R, Helmut, M, Anne, R, Solin, O & Pirjo, N 2014, '64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats', Molecular Imaging and Biology, vol. 16, nr. 2, s. 255–263. https://doi.org/10.1007/s11307-013-0691-2

TY - JOUR

T1 - 64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats

AU - Kirsi, Mikkola

AU - Yim, Cheng-Bin

AU - Veronica, Fagerholm

AU - Tamiko, Ishizu

AU - Elomaa, Viki-Veikko

AU - Rajander, Johan

AU - Jori, Jurttila

AU - Tiina, Saanijoki

AU - Tuula, Tolvanen

AU - Marko, Tirri

AU - Eleni, Gourni

AU - Martin, Béhé

AU - Martin, Gotthardt

AU - Jean Claude, Reubi

AU - Helmut, Mäcke

AU - Anne, Roivainen

AU - Solin, Olof

AU - Pirjo, Nuutila

PY - 2014

Y1 - 2014

N2 - Purpose Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle14,Lys40(Ahx-NODAGA-64Cu)NH2]-exendin-4 ([64Cu]NODAGA-exendin-4) and [Nle14,Lys40(Ahx-NODAGA-68Ga)NH2]-exendin-4 ([68Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents. Procedures The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated. Results We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [64Cu]NODAGA-exendin-4 and [68Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively. Conclusion [64Cu]NODAGA-exendin-4 might be more effective for labelling islets than [68Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [68Ga]NODAGA-exendin-4 compared to [64Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [64Cu]NODAGA-exendin-4 as a clinical tracer.

AB - Purpose Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for imaging of pancreatic beta cells. We compared the ability of [Nle14,Lys40(Ahx-NODAGA-64Cu)NH2]-exendin-4 ([64Cu]NODAGA-exendin-4) and [Nle14,Lys40(Ahx-NODAGA-68Ga)NH2]-exendin-4 ([68Ga]NODAGA-exendin-4) to detect native pancreatic islets in rodents. Procedures The stability, lipophilicity and affinity of the radiotracers to the GLP-1R were determined in vitro. The biodistribution of the tracers was assessed using autoradiography, ex vivo biodistribution and PET imaging. Estimates for human radiation dosimetry were calculated. Results We found GLP-1R-specific labelling of pancreatic islets. However, the pancreas could not be visualised in PET images. The highest uptake of the tracers was observed in the kidneys. Effective dose estimates for [64Cu]NODAGA-exendin-4 and [68Ga]NODAGA-exendin-4 were 0.144 and 0.012 mSv/MBq, respectively. Conclusion [64Cu]NODAGA-exendin-4 might be more effective for labelling islets than [68Ga]NODAGA-exendin-4. This is probably due to the lower specific radioactivity of [68Ga]NODAGA-exendin-4 compared to [64Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of [64Cu]NODAGA-exendin-4 as a clinical tracer.

U2 - 10.1007/s11307-013-0691-2

DO - 10.1007/s11307-013-0691-2

M3 - Artikel

SN - 1536-1632

VL - 16

SP - 255

EP - 263

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 2

ER -