Skip to main content
SpringerLink
Log in

Twins in spirit part II: DOTATATE and high-affinity DOTATATE—the clinical experience

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Over recent decades interest in diagnosis and treatment of neuroendocrine tumours (NET) has steadily grown. The basis for diagnosis and therapy of NET with radiolabelled somatostatin (hsst) analogues is the variable overexpression of hsst receptors (hsst1–5 receptors). We hypothesized that radiometal derivatives of DOTA-iodo-Tyr3-octreotide analogues might be excellent candidates for somatostatin receptor imaging. We therefore explored the diagnostic potential of 68Ga-DOTA-iodo-Tyr3-octreotate [68Ga-DOTA,3-iodo-Tyr3,Thr8]octreotide (68Ga-HA-DOTATATE; HA, high-affinity) compared to the established 68Ga-DOTA-Tyr3-octreotate (68Ga-DOTATATE) in vivo.

Methods

The study included 23 patients with known somatostatin receptor-positive metastases from NETs, thyroid cancer or glomus tumours who were investigated with both 68Ga-HA-DOTATATE and 68Ga-DOTATATE. A patient-based and a lesion-based comparative analysis was carried out of normal tissue distribution and lesion detectability in a qualitative and a semiquantitative manner.

Results

68Ga-HA-DOTATATE and 68Ga-DOTATATE showed comparable uptake in the liver (SUVmean 8.9 ± 2.2 vs. 9.3 ± 2.5, n.s.), renal cortex (SUVmean 13.3 ± 3.9 vs. 14.5 ± 3.7, n.s.) and spleen (SUVmean 24.0 ± 6.7 vs. 22.9 ± 7.3, n.s.). A somewhat higher pituitary uptake was found with 68Ga-HA-DOTATATE (SUVmean 6.3 ± 1.8 vs. 5.4 ± 2.1, p < 0.05). On a lesion-by-lesion basis a total of 344 lesions were detected. 68Ga-HA-DOTATATE demonstrated 328 lesions (95.3 % of total lesions seen), and 68Ga-DOTATATE demonstrated 332 lesions (96.4 %). The mean SUVmax of all lesions was not significantly different between 68Ga-HA-DOTATATE and 68Ga-DOTATATE (17.8 ± 11.4 vs. 16.7 ± 10.7, n.s.).

Conclusion

Our analysis demonstrated very good concordance between 68Ga-HA-DOTATATE and 68Ga-DOTATATE PET data. As the availability and use of 68Ga-HA-DOTATATE is not governed by patent restrictions it may be an attractive alternative to other 68Ga-labelled hsst analogues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Atkinson H, England JA, Rafferty A, Jesudason V, Bedford K, Karsai L, et al. Somatostatin receptor expression in thyroid disease. Int J Exp Pathol. 2013;94:226–9. doi:10.1111/iep.12024.

    Article  CAS  PubMed  Google Scholar 

  2. Kaemmerer D, Peter L, Lupp A, Schulz S, Sanger J, Prasad V, et al. Molecular imaging with 68Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38:1659–68. doi:10.1007/s00259-011-1846-5.

    Article  CAS  PubMed  Google Scholar 

  3. Lamberts SW, Bakker WH, Reubi JC, Krenning EP. Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med. 1990;323:1246–9.

    Article  CAS  PubMed  Google Scholar 

  4. Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0), Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2003;30:417–22. doi:10.1007/s00259-002-1050-8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Krenning EP, Bakker WH, Breeman WA, Koper JW, Kooij PP, Ausema L, et al. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet. 1989;1:242–4.

    Article  CAS  PubMed  Google Scholar 

  6. Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging. 2010;37:2004–10. doi:10.1007/s00259-010-1512-3.

    Article  PubMed  Google Scholar 

  7. Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000;27:273–82.

    Article  CAS  PubMed  Google Scholar 

  8. Ginj M, Schmitt JS, Chen J, Waser B, Reubi JC, de Jong M, et al. Design, synthesis, and biological evaluation of somatostatin-based radiopeptides. Chem Biol. 2006;13:1081–90. doi:10.1016/j.chembiol.2006.08.012.

    Article  CAS  PubMed  Google Scholar 

  9. Brogsitter C, Schottelius M, Zophel K, Kotzerke J, Wester HJ. Twins in spirit: DOTATATE and high-affinity DOTATATE. Eur J Nucl Med Mol Imaging. 2013;40:1789. doi:10.1007/s00259-013-2497-5.

    Article  PubMed  Google Scholar 

  10. Krenning EP, Bakker WH, Kooij PP, Breeman WA, Oei HY, de Jong M, et al. Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J Nucl Med. 1992;33:652–8.

    CAS  PubMed  Google Scholar 

  11. Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schafer M, et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2007;34:1617–26. doi:10.1007/s00259-007-0450-1.

    Article  CAS  PubMed  Google Scholar 

  12. Hartmann H, Zophel K, Freudenberg R, Oehme L, Andreeff M, Wunderlich G, et al. Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations. Nuklearmedizin. 2009;48:201–7. doi:10.3413/nukmed-0214.

    CAS  PubMed  Google Scholar 

  13. Kowalski J, Henze M, Schuhmacher J, Macke HR, Hofmann M, Haberkorn U. Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D Phe(1)-Tyr(3)-Octreotide in comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors. Mol Imaging Biol. 2003;5:42–8.

    Article  PubMed  Google Scholar 

  14. Virgolini IJ, Gabriel M, von Guggenberg E, Putzer D, Kendler D, Decristoforo C. Role of radiopharmaceuticals in the diagnosis and treatment of neuroendocrine tumours. Eur J Cancer. 2009;45 Suppl 1:274–91. doi:10.1016/S0959-8049(09)70042-5.

    Article  PubMed  Google Scholar 

  15. Ben-Shlomo A, Melmed S. Pituitary somatostatin receptor signaling. Trends Endocrinol Metab. 2010;21:123–33. doi:10.1016/j.tem.2009.12.003.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Hofland LJ, Feelders RA, de Herder WW, Lamberts SW. Pituitary tumours: the sst/D2 receptors as molecular targets. Mol Cell Endocrinol. 2010;326:89–98. doi:10.1016/j.mce.2010.04.020.

    Article  CAS  PubMed  Google Scholar 

  17. Kabasakal L, Demirci E, Ocak M, Decristoforo C, Araman A, Ozsoy Y, et al. Comparison of 68Ga-DOTATATE and 68Ga-DOTANOC PET/CT imaging in the same patient group with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2012;39:1271–7.

    Article  PubMed  Google Scholar 

  18. Poeppel TD, Binse I, Petersenn S, Lahner H, Schott M, Antoch G, et al. 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. J Nucl Med. 2011;52:1864–70.

    Article  CAS  PubMed  Google Scholar 

  19. Wild D, Bomanji JB, Benkert P, Maecke H, Ell PJ, Reubi JC, et al. Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT within patients with gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2013;54:364–72.

    Article  CAS  PubMed  Google Scholar 

  20. Putzer D, Kroiss A, Waitz D, Gabriel M, Traub-Weidinger T, Uprimny C, et al. Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0, Tyr3-octreotide versus 68Ga-DOTA0-lanreotide. Eur J Nucl Med Mol Imaging. 2013;40:364–72. doi:10.1007/s00259-012-2286-6.

    Article  CAS  PubMed  Google Scholar 

  21. Demirci E, Ocak M, Kabasakal L, Araman A, Ozsoy Y, Kanmaz B. Comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-LAN PET/CT imaging in the same patient group with neuroendocrine tumours: preliminary results. Nucl Med Commun. 2013;34:727–32. doi:10.1097/MNM.0b013e328362cca6.

    Article  CAS  PubMed  Google Scholar 

  22. Naswa N, Sharma P, Suman Kc S, Lata S, Kumar R, Malhotra A, et al. Prospective evaluation of 68Ga-DOTA-NOC PET-CT in patients with recurrent medullary thyroid carcinoma: comparison with 18F-FDG PET-CT. Nucl Med Commun. 2012;33:766–74. doi:10.1097/MNM.0b013e3283541157.

    Article  PubMed  Google Scholar 

  23. Shastry M, Kayani I, Wild D, Caplin M, Visvikis D, Gacinovic S, et al. Distribution pattern of 68Ga-DOTATATE in disease-free patients. Nucl Med Commun. 2010;31:1025–32.

    PubMed  Google Scholar 

  24. Vanhagen PM, Krenning EP, Reubi JC, Kwekkeboom DJ, Bakker WH, Mulder AH, et al. Somatostatin analogue scintigraphy in granulomatous diseases. Eur J Nucl Med. 1994;21:497–502.

    Article  CAS  PubMed  Google Scholar 

  25. Mussig K, Oksuz MO, Pfannenberg C, Adam P, Zustin J, Beckert S, et al. Somatostatin receptor expression in an epitheloid hemangioma causing oncogenic osteomalacia. J Clin Endocrinol Metab. 2009;94:4123–4.

    Article  PubMed  Google Scholar 

  26. Winter PF, Lapke J, Winek R. Subcutaneous cavernous hemangioma visualized on an indium-111-octreotide scan. J Nucl Med. 1996;37:1516–7.

    CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

H.J. Wester is CEO of SCINTOMICS, Germany, but without any conflicts of interest. The other authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany

    Claudia Brogsitter, Klaus Zöphel, Holger Hartmann & Jörg Kotzerke

  2. Pharmaceutical Radiochemistry and Department of Nuclear Medicine, Technische Universität München, München, Germany

    Margret Schottelius & Hans-Jürgen Wester

Authors
  1. Claudia Brogsitter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Zöphel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Holger Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Margret Schottelius
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans-Jürgen Wester
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jörg Kotzerke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudia Brogsitter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brogsitter, C., Zöphel, K., Hartmann, H. et al. Twins in spirit part II: DOTATATE and high-affinity DOTATATE—the clinical experience. Eur J Nucl Med Mol Imaging 41, 1158–1165 (2014). https://doi.org/10.1007/s00259-014-2690-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-014-2690-1

Keywords

Search

Navigation