open access

https://hdl.handle.net/2115/98009

Synthesis and preclinical evaluation of a 68Ga-labeled peptide for PET imaging of transferrin receptor 1 in tumor

英語

Cysteine-dense peptide

2025-08-08

Springer

European Journal of Nuclear Medicine and Molecular Imaging

53(1)

687-696

Purpose Transferrin receptor 1 (TfR1) is a transmembrane glycoprotein that mediates cellular iron uptake. Despite its potential as a target for tumor diagnosis, the lack of suitable TfR1 ligands has hindered the development of effective TfR1 imaging agents. We labeled a recently discovered TfR1 ligand, TfRB1G3, with Ga-68 and evaluated its potential for TfR1 imaging through preclinical experiments. Methods TfRB1G3 was modified with HBED-CC and radiolabeled with Ga-67/68 ([Ga-67/68]Ga-TfRB1G3). Human glioblastoma (U87MG) cells were transfected with TfR1-targeting siRNA (TfR1-knockdown) or non-targeting siRNA (control), and accumulation of [Ga-67]Ga-TfRB1G3 was evaluated. The K-D value of [Ga-67]Ga-TfRB1G3 for TfR1 was also calculated. Ex vivo biodistribution was conducted in normal and U87MG tumor-bearing mice after injecting [Ga-67]Ga-TfRB1G3. PET imaging studies were conducted after injecting [Ga-68]Ga-TfRB1G3, with/without co-injection of 10 nmol TfRB1G3 in mice bearing U87MG tumors. Results [Ga-67/68]Ga-TfRB1G3 was obtained with high radiochemical purity (> 90%). The accumulation of [Ga-67]Ga-TfRB1G3 in the TfR1-knockdown cells (22.0 +/- 1.1% Dose/mg) was significantly lower than that in the control (308.5 +/- 14.3% Dose/mg). The K-D value was 1.0 nM. Tumor accumulation of [Ga-67]Ga-TfRB1G3 was higher than in any other organs except the kidneys, and co-injection of TfRB1G3 significantly reduced the tumor accumulation by more than 90%. PET imaging with [Ga-68]Ga-TfRB1G3 clearly visualized TfR1-positive tumor as early as 20 min post-injection. Conclusion [Ga-68]Ga-TfRB1G3 demonstrated excellent affinity and specificity for TfR1 both in vitro and in vivo, providing clear PET images of TfR1-positive tumors shortly after injection. [Ga-68]Ga-TfRB1G3 would enable sensitive and quantitative imaging of TfR1 expression.

学術雑誌論文

Accepted Manuscript

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00259-025-07493-8

1619-7070

1619-7089