Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

P Antunes, M Ginj, H Zhang, B Waser, R P Baum, J C Reubi, H Maecke, P Antunes, M Ginj, H Zhang, B Waser, R P Baum, J C Reubi, H Maecke

Abstract

Purpose: Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [68Ga-DOTA,Tyr3]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its 111In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority.

Methods: Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J.

Results: All peptides showed high affinities on hsst2, with the highest affinity for the Ga(III)-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the Ga(III) peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all 67Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the 111In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [67Ga-DOTA,1-Nal3]octreotide in comparison to [111In-DOTA,1-Nal3]octreotide and [67Ga-DOTA,Tyr3]octreotide showed a significantly higher and receptor-mediated uptake of the two 67Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide.

Conclusion: This study demonstrates that 67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies.

References

    1. Eur J Nucl Med Mol Imaging. 2003 Jan;30(1):117-22
    1. J Nucl Med. 2005 Jan;46 Suppl 1:62S-6S
    1. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):897-903
    1. Eur J Nucl Med Mol Imaging. 2006 Apr;33(4):506
    1. J Nucl Med. 2006 May;47(5):793-6
    1. J Nucl Med. 2001 Jul;42(7):1053-6
    1. J Biol Chem. 2004 May 14;279(20):21374-82
    1. Eur J Nucl Med. 2000 Sep;27(9):1318-25
    1. Curr Opin Oncol. 2000 Jul;12(4):368-77
    1. J Med Chem. 2004 Mar 11;47(6):1465-74
    1. Eur J Nucl Med. 1997 Apr;24(4):368-71
    1. Int J Cancer. 2001 Jun 1;92(5):628-33
    1. Eur J Nucl Med. 2000 Mar;27(3):273-82
    1. Mol Imaging Biol. 2003 Jan-Feb;5(1):42-8
    1. Eur J Nucl Med Mol Imaging. 2004 Mar;31(3):466
    1. J Nucl Med. 1994 Feb;35(2):317-25
    1. Eur J Nucl Med Mol Imaging. 2003 Oct;30(10):1338-47
    1. J Nucl Med. 2002 May;43(5):610-6
    1. Eur J Nucl Med Mol Imaging. 2006 Jul;33(7):823-30
    1. J Nucl Med. 2005 May;46(5):763-9
    1. Bioconjug Chem. 2002 May-Jun;13(3):530-41
    1. Clin Cancer Res. 2004 Dec 15;10(24):8674-82
    1. Nat Biotechnol. 2004 Jun;22(6):701-6
    1. J Nucl Med. 2005 Jan;46 Suppl 1:172S-8S
    1. Endocr Rev. 2003 Aug;24(4):389-427
    1. J Nucl Med. 2005 Sep;46(9):1561-9
    1. Eur J Nucl Med Mol Imaging. 2004 Dec;31(12):1653-7
    1. Eur J Nucl Med Mol Imaging. 2005 Jun;32(6):724
    1. Eur J Nucl Med Mol Imaging. 2003 Feb;30(2):207-16
    1. Lancet. 1998 Feb 7;351(9100):417-8
    1. Eur J Nucl Med. 1993 Aug;20(8):716-31
    1. J Inorg Biochem. 2004 Nov;98(11):1874-901
    1. Clin Cancer Res. 2005 Feb 1;11(3):1136-45
    1. Eur J Nucl Med. 2001 Dec;28(12):1751-7
    1. J Nucl Med. 2006 Mar;47(3):502-11
    1. Eur J Nucl Med Mol Imaging. 2002 Jun;29(6):742-53
    1. Semin Nucl Med. 2006 Jul;36(3):228-47
    1. J Nucl Med. 2005 Jul;46(7):1210-8
    1. Int J Cancer. 2002 Apr 20;98(6):930-7

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다