The purpose of this study is to develop peptide-based platelet-derived growth factor receptor β (PDGFRβ) imaging probes and examine the effects of several linkers, namely un-natural amino acids (D-alanine and β-alanine) and ethylene-glycol (EG), on the properties of Ga-DOTA(linker)-IPLPPPRRPFFK peptides. Seven radiotracers,67 Ga-DOTA-(linker)-IPLPPPRRPFFK peptides, were designed, synthesized, and evaluated. The stability and cell uptake in PDGFRβ positive peptide cells were evaluated in vitro. The biodistribution of [67 Ga]Ga-DOTA-EG2-IPLPPPRRPFFK ([67 Ga]27) and [67 Ga]Ga-DOTA-EG4-IPLPPPRRPFFK ([67 Ga]28), which were selected based on in vitro stability in murine plasma and cell uptake rates, were determined in BxPC3-luc-bearing nu/nu mice. Seven67 Ga-labeled peptides were successfully synthesized with high radiochemical yields (>85%) and purities (>99%). All evaluated radiotracers were stable in PBS (pH 7.4) at 37◦ C. However, only [67 Ga]27 and [67 Ga]28 remained more than 75% after incubation in murine plasma at 37◦ C for 1 h. [67 Ga]27 exhibited the highest BxPC3-luc cell uptake among the prepared radiolabeled peptides. As regards the results of the biodistribution experiments, the tumor-to-blood ratios of [67 Ga]27 and [67 Ga]28 at 1 h post-injection were 2.61 ± 0.75 and 2.05 ± 0.77, respectively. Co-injection of [67 Ga]27 and an excess amount of IPLPPPRRPFFK peptide as a blocking agent can significantly decrease this ratio. However, tumor accumulation was not considered sufficient. Therefore, further probe modification is required to assess tumor accumulation for in vivo imaging.
CITATION STYLE
Effendi, N., Mishiro, K., Shiba, K., Kinuya, S., & Ogawa, K. (2021). Development of radiogallium-labeled peptides for platelet-derived growth factor receptor β (Pdgfrβ) imaging: Influence of different linkers. Molecules, 26(1). https://doi.org/10.3390/molecules26010041
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