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Background <p>Gastrin-releasing peptide receptor (GRPR) attracts increasing attention as a target for radiotheranostic applications. We previously developed a metabolically stable GRPR-targeting peptide, incorporating α-methyl-L-tryptophan within its sequence (PEG<sub>2</sub>-Pip-D-Phe<sup>6</sup>-Gln<sup>7</sup>-MetTrp<sup>8</sup>-Ala<sup>9</sup>-Val<sup>10</sup>-Sar<sup>11</sup>-His<sup>12</sup>-Sta<sup>13</sup>-Leu<sup>14</sup>-NH<sub>2</sub>) and coupled it to DOTAGA chelator (PKB2) and to DOTA (PKB3). When labelled with Lu-177, both peptide variants demonstrated promising properties for targeted radionuclide therapy.</p> Results <p>In this study, we aimed to evaluate the diagnostic counterparts of PKB2 and PKB3 by radiolabelling them with Ga-68 for positron emission tomography (PET) imaging. [<sup>68</sup>Ga]Ga-PKB2 and [<sup>68</sup>Ga]Ga-PKB3 were produced with radiochemical yields over 99% and radiochemical purities over 97%. Both radiopeptides showed a high GRPR affinity with IC<sub>50</sub> values in the low nanomolar range and a GRPR-mediated uptake in PC-3 cells with slow internalization. The labelled peptides [<sup>68</sup>Ga]Ga-PKB2 and [<sup>68</sup>Ga]Ga-PKB3 demonstrated fast clearance with activity concentration in blood below 0.5%IA/g at 2&#xa0;pi, and a high tumour activity uptake in PC-3 xenografts (16 ± 3%IA/g and 17 ± 2%IA/g, respectively). [<sup>68</sup>Ga]Ga-PKB3 had a significantly higher activity uptake in the pancreas (GRPR-expressing organ) and lower uptake in the kidneys than [<sup>68</sup>Ga]Ga-PKB2. PET/CT images were concordant with the biodistribution results, clearly delineating tumour tissue.</p> Conclusions <p>[<sup>68</sup>Ga]Ga-PKB2 and [<sup>68</sup>Ga]Ga-PKB3 are promising PET tracers for imaging of GRPR-positive tumours and are potential diagnostic counterparts to their <sup>177</sup>Lu-labelled analogues, supporting their use as a <sup>177</sup>Lu/<sup>68</sup>Ga theranostic pair.</p>

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Exploring the theranostic potential of two metabolically stable GRPR-targeting peptides labelled with Ga-68 for PET imaging

  • 期刊论文

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  • 发表日期：

    2026年2月17日

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  • Karim Obeid,
  • Ekaterina Bezverkhniaia,
  • Vladimir Tolmachev,
  • Anna Orlova,
  • Panagiotis Kanellopoulos

摘要

Background

Gastrin-releasing peptide receptor (GRPR) attracts increasing attention as a target for radiotheranostic applications. We previously developed a metabolically stable GRPR-targeting peptide, incorporating α-methyl-L-tryptophan within its sequence (PEG2-Pip-D-Phe6-Gln7-MetTrp8-Ala9-Val10-Sar11-His12-Sta13-Leu14-NH2) and coupled it to DOTAGA chelator (PKB2) and to DOTA (PKB3). When labelled with Lu-177, both peptide variants demonstrated promising properties for targeted radionuclide therapy.

Results

In this study, we aimed to evaluate the diagnostic counterparts of PKB2 and PKB3 by radiolabelling them with Ga-68 for positron emission tomography (PET) imaging. [68Ga]Ga-PKB2 and [68Ga]Ga-PKB3 were produced with radiochemical yields over 99% and radiochemical purities over 97%. Both radiopeptides showed a high GRPR affinity with IC50 values in the low nanomolar range and a GRPR-mediated uptake in PC-3 cells with slow internalization. The labelled peptides [68Ga]Ga-PKB2 and [68Ga]Ga-PKB3 demonstrated fast clearance with activity concentration in blood below 0.5%IA/g at 2 pi, and a high tumour activity uptake in PC-3 xenografts (16 ± 3%IA/g and 17 ± 2%IA/g, respectively). [68Ga]Ga-PKB3 had a significantly higher activity uptake in the pancreas (GRPR-expressing organ) and lower uptake in the kidneys than [68Ga]Ga-PKB2. PET/CT images were concordant with the biodistribution results, clearly delineating tumour tissue.

Conclusions

[68Ga]Ga-PKB2 and [68Ga]Ga-PKB3 are promising PET tracers for imaging of GRPR-positive tumours and are potential diagnostic counterparts to their 177Lu-labelled analogues, supporting their use as a 177Lu/68Ga theranostic pair.