Bispecific GRPR-antagonistic anti-PSMA/GRPR heterodimer for PET and SPECT diagnostic imaging of prostate cancer

Bogdan Mitran, Zohreh Varasteh, Ayman Abouzayed, Sara S. Rinne, Emmi Puuvuori, Maria De Rosa, Mats Larhed, Vladimir Tolmachev, Anna Orlova, Ulrika Rosenström

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Simultaneous targeting of the prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) could improve the diagnostic accuracy in prostate cancer (PCa). The aim of this study was to develop a PSMA/GRPR-targeting bispecific heterodimer for SPECT and positron emission tomography (PET) diagnostic imaging of PCa. The heterodimer NOTA-DUPA-RM26 was produced by manual solid-phase peptide synthesis. NOTA-DUPA-RM26 was labeled with111In and68Ga, with yields >98%, and demonstrated a high stability and binding specificity to PSMA and GRPR. IC50 values fornat In-NOTA-DUPA-RM26 were 4 ± 1 nM towards GRPR and 824 ± 230 nM towards PSMA. An in vivo binding specificity 1 h pi of111In-NOTA-DUPA-RM26 in PC3-PIP-xenografted mice demonstrated partially blockable tumor uptake when co-injected with an excess of PSMA-or GRPR-targeting agents. Simultaneous co-injection of both agents induced pronounced blocking. The biodistribution of111In-NOTA-DUPA-RM26 and68Ga-NOTA-DUPA-RM26 revealed fast activity clearance from the blood and normal organs via the kidneys. Tumor uptake exceeded normal organ uptake for both analogs 1 h pi.68Ga-NOTA-DUPA-RM26 had a significantly lower tumor uptake (8 ± 2%ID/g) compared to111In-NOTA-DUPA-RM26 (12 ± 2%ID/g) 1 h pi. Tumor-to-organ ratios increased 3 h pi, but decreased 24 h pi, for111In-NOTA-DUPA-RM26. MicroPET/CT and microSPECT/CT scans confirmed biodistribution data, suggesting that68Ga-NOTA-DUPA-RM26 and111In-NOTA-DUPA-RM26 are suitable candidates for the imaging of GRPR and PSMA expression in PCa shortly after administration.

Original languageEnglish
Article number1371
Issue number9
Publication statusPublished - Sep 2019
Externally publishedYes


  • GRPR
  • Heterodimer
  • Molecular imaging
  • PET
  • Prostate cancer
  • PSMA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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