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99mTc-Demotate 1: first data in tumour patients—results of a pilot/phase I study

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Abstract

Somatostatin receptor (SSTR) scintigraphy with indium-111 DTPA-octreotide has become a routine diagnostic procedure in oncology. However, it suffers some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of 111In. We have recently been involved in the development of a new tetraamine-functionalised [Tyr3]octreotate derivative (Demotate 1) that can be easily labelled with technetium-99m at high specific activities. 99mTc-Demotate 1 showed promising properties in preclinical studies. In this study we report on the first experience with 99mTc-Demotate 1 in patients. Six patients (mean age 56 years) with carcinoid tumours (n=2) or endocrine pancreatic tumours (n=4) with previously positive SSTR scintigraphy were enrolled in the study. Patients were injected with 500–600 MBq 99mTc-Demotate 1. Clinical and laboratory parameters were controlled up to 3 months p.i. Blood samples were taken at various time points up to 24 h p.i., and urine was collected up to 24 h. Whole-body images were acquired at 15–30 min, 1–2 h, 4 h and 24 h p.i. with additional single-photon emission tomography imaging at 1–4 h. Blood excretion was very rapid, with <2%ID in plasma after 1 h, and urinary excretion <20% ID after 6 h. Two patients complained of mild gastrointestinal problems and paraesthesia, but no other adverse reactions were observed. SSTR-positive tumours were rapidly visualised as early as 15 min p.i., with maximum tumour uptake (up to 19% ID) and tumour/organ ratios as early as 1 h p.i. Organs of predominant physiological uptake were the spleen and the kidneys, with no intestinal excretion detectable up to 24 h. 99mTc-Demotate 1 detected 11 lesions while In-Oct detected ten; differences in uptake behaviour were observed in three patients. This study shows for the first time that peptides derivatised with a tetraamine ligand for labelling with 99mTc show suitable properties for receptor imaging in patients. 99mTc-Demotate 1 is a promising agent for the visualisation of SSTR-positive lesions in patients, allowing rapid imaging as early as 1 h p.i.; some differences are observed in pharmacokinetic behaviour compared with 111In-DTPA-octreotide.

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Acknowledgements

We especially wish to thank Prof. E. Chiotellis, University of Thessaloniki, and Prof. G. Riccabona, Prof. Emeritus, University of Innsbruck, for their help and support in initiating this study. Cooperation between Athens and Innsbruck was intensified by the participation in the COST B12 programme: "Radiotracers for in vivo assessment of biological function", WG-3: "Radiolabelled biologically active peptides", supported by the EU.

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Authors and Affiliations

  1. Univ.-Klinik fuer Nuklearmedizin, Anichstrasse 35, 6020, Innsbruck, Austria

    Clemens Decristoforo, Michael Gabriel & Roy Moncayo

  2. Institute of Radioisotopes—Radiodiagnostic Products, National Center for Scientific Research "Demokritos", Attikis, Athens, Greece

    Theodosia Maina & Berthold Nock

  3. Department of Pharmacy, University of Patras, Patras, Greece

    Paul Cordopatis

Authors
  1. Clemens Decristoforo
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  2. Theodosia Maina
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  3. Berthold Nock
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  4. Michael Gabriel
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  5. Paul Cordopatis
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  6. Roy Moncayo
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Correspondence to Clemens Decristoforo.

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Decristoforo, C., Maina, T., Nock, B. et al. 99mTc-Demotate 1: first data in tumour patients—results of a pilot/phase I study. Eur J Nucl Med Mol Imaging 30, 1211–1219 (2003). https://doi.org/10.1007/s00259-003-1225-y

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  • DOI: https://doi.org/10.1007/s00259-003-1225-y

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