Preparation and preclinical evaluation of a 68Ga-labelled c(RGDfK) conjugate comprising the bifunctional chelator NODIA-Me

Läppchen, Tilman; Holland, Jason P.; Kiefer, Yvonne; Bartholomä, Mark D. (2018). Preparation and preclinical evaluation of a 68Ga-labelled c(RGDfK) conjugate comprising the bifunctional chelator NODIA-Me. EJNMMI Radiopharmacy and Chemistry, 3(1), p. 6. Springer 10.1186/s41181-018-0043-2

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Background: We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three, five-membered azaheterocyclic arms for the development of 68Ga- and 64Cu-based radiopharmaceuticals. Here, a 68Ga-labelled conjugate comprising the bifunctional chelator NODIA-Me in combination with the αvß3-targeting peptide c(RGDfK) has been synthesized and characterized. The primary aim was to evaluate further the potential of our NODIA-Me chelating system for the development of 68Ga-labelled radiotracers. Results: The BFC NODIA-Me was conjugated to c(RGDfK) by standard peptide chemistry to obtain the final bioconjugate NODIA-Me-c(RGDfK) 3 in 72% yield. Labelling with [68Ga]GaCl3 was accomplished in a fully automated, cGMP compliant process to give [68Ga]3 in high radiochemical yield (98%) and moderate specific activity (~ 8 MBq nmol- 1). Incorporation of the Ga-NODIA-Me chelate to c(RGDfK) 2 had only minimal influence on the affinity to integrin αvß3 (IC50 values [natGa]3 = 205.1 ± 1.4 nM, c(RGDfK) 2 = 159.5 ± 1.3 nM) as determined in competitive cell binding experiments in U-87 MG cell line. In small-animal PET imaging and ex vivo biodistribution studies, the radiotracer [68Ga]3 showed low uptake in non-target organs and specific tumor uptake in U-87 MG tumors. Conclusion: The results suggest that the bifunctional chelator NODIA-Me is an interesting alternative to existing ligands for the development of 68Ga-labelled radiopharmaceuticals.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine

UniBE Contributor:

Läppchen, Tilman

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2365-421X

Publisher:

Springer

Language:

English

Submitter:

Sabine Lanz

Date Deposited:

01 Feb 2019 15:32

Last Modified:

02 Dec 2019 20:34

Publisher DOI:

10.1186/s41181-018-0043-2

PubMed ID:

29756024

Uncontrolled Keywords:

Bifunctional chelator; Gallium-68; Integrins; NODIA-Me; PET imaging; αvß3

BORIS DOI:

10.7892/boris.125634

URI:

https://boris.unibe.ch/id/eprint/125634

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