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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.07.2006 | Original article

[^99mTc]Demotate 2 in the detection of sst₂-positive tumours: a preclinical comparison with [¹¹¹In]DOTA-tate

verfasst von: Theodosia Maina, Berthold A. Nock, Paul Cordopatis, Bert F. Bernard, Wout A. P. Breeman, Arthur van Gameren, Ria van den Berg, Jean-Claude Reubi, Eric P. Krenning, Marion de Jong

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 7/2006

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Abstract

Purpose

The aim of this study was to evaluate [^99mTc]Demotate 2 ([^99mTc-N₄ ^0-1,Asp⁰,Tyr³]octreotate) as a candidate for in vivo imaging of sst₂-positive tumours and to compare it with [¹¹¹In]DOTA-tate ([¹¹¹In-DOTA⁰,Tyr³]octreotate).

Methods

Labelling of Demotate 2 with ^99mTc was performed at room temperature using SnCl₂ as reductant in the presence of citrate at alkaline pH. Radiochemical analysis involved ITLC and HPLC methods. Peptide conjugate affinities for sst₂ were determined by receptor autoradiography on rat brain cortex sections using [DOTA⁰,¹²⁵I-Tyr³]octreotate as the radioligand. The affinity profile of Demotate 2 for human sst₁–sst₅ was studied by receptor autoradiography in cell preparations using the universal somatostatin radioligand [¹²⁵I][Leu⁸,(D)Trp²²,Tyr²⁵]somatostatin-28. The internalisation rates of [^99mTc]Demotate 2 and [¹¹¹In]DOTA-tate were compared in sst₂-positive and -negative control cell lines. Biodistribution of radiopeptides was studied in male Lewis rats bearing CA20948 tumours.

Results

Peptide conjugates showed selectivity and a high affinity binding for sst₂ (Demotate 2 IC₅₀=3.2 nM and DOTA-tate IC₅₀=5.4 nM). [^99mTc]Demotate 2, like [¹¹¹In]DOTA-tate, internalised rapidly in all sst₂-positive cells tested, but not in sst₂-negative control cells. After injection in CA20948 tumour-bearing rats both radiopeptides showed high and specific uptake in the sst₂-positive organs and in the implanted tumour and rapid excretion from non-target tissues via the kidneys.

Conclusion

[^99mTc]Demotate 2, similarly to the known sst₂-targeting agent [¹¹¹In]DOTA-tate, showed promising biological qualities for application in the scintigraphy of sst₂-positive tumours.

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Titel: [99mTc]Demotate 2 in the detection of sst2-positive tumours: a preclinical comparison with [111In]DOTA-tate
verfasst von: Theodosia Maina
Berthold A. Nock
Paul Cordopatis
Bert F. Bernard
Wout A. P. Breeman
Arthur van Gameren
Ria van den Berg
Jean-Claude Reubi
Eric P. Krenning
Marion de Jong
Publikationsdatum: 01.07.2006
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 7/2006
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0068-8

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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