Advertisement

68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT

  • A. KroissEmail author
  • D. Putzer
  • C. Decristoforo
  • C. Uprimny
  • B. Warwitz
  • B. Nilica
  • M. Gabriel
  • D. Kendler
  • D. Waitz
  • G. Widmann
  • I. J. Virgolini
Original Article

Abstract

Purpose

We wanted to establish the range of 68Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT).

Methods

In 249 patients, 390 68Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies).

Results

SUVmax (mean ± standard deviation) values of 68Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUVmax between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUVmax for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001).

Conclusion

68Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

Keywords

68Ga-DOTA-TOC Neuroendocrine tumours SUVmax 

Notes

Acknowledgments

We are grateful to Mathias Wochinz from the Department of Nuclear Medicine (Innsbruck Medical University, Austria) for his work on the project. The authors thank Regina Figl and Barry Shulkin for their editorial assistance and Harald Kühschelm for statistical advice. We also thank Gregory Minear for technical advice.

Conflicts of interest

None.

References

  1. 1.
    Reubi JC, Waser B, Schaer JC, Laissue JA. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001;28:836–46.PubMedCrossRefGoogle Scholar
  2. 2.
    Reubi JC, Schaer 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.PubMedCrossRefGoogle Scholar
  3. 3.
    Rodrigues M, Traub-Weidinger T, Leimer M, Li S, Andreae F, Angelberger P, et al. Value of 111In-DOTA-lanreotide and 111In-DOTA-DPhe1-Tyr3-octreotide in differentiated thyroid cancer: results of in vitro binding studies and in vivo comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging. 2005;32:1144–51.PubMedCrossRefGoogle Scholar
  4. 4.
    Kwekkeboom DJ, Kooij PP, Bakker WH, Mäcke HR, Krenning EP. Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake. J Nucl Med. 1999;40:762–7.PubMedGoogle Scholar
  5. 5.
    Baum RP, Prasad V, Hommann M, Hörsch D. Receptor PET/CT imaging of neuroendocrine tumors. Recent Results Cancer Res. 2008;170:225–42.PubMedCrossRefGoogle Scholar
  6. 6.
    Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007;48:508–18.PubMedCrossRefGoogle Scholar
  7. 7.
    Putzer D, Gabriel M, Henninger B, Kendler D, Uprimny C, Dobrozemsky G, et al. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy. J Nucl Med. 2009;50:1214–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Boy C, Heusner TA, Poeppel TD, Redmann-Bischofs A, Unger N, Jentzen W, et al. 68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax. Eur J Nucl Med Mol Imaging. 2011;38:1224–36.PubMedCrossRefGoogle Scholar
  9. 9.
    Decristoforo C, Knopp R, von Guggenberg E, Rupprich M, Dreger T, Hess A, et al. A fully automated synthesis for the preparation of 68Ga-labelled peptides. Nucl Med Commun. 2007;28:870–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Prasad V, Baum RP. Biodistribution of the Ga-68 labeled somatostatin analogue DOTA-NOC in patients with neuroendocrine tumors: characterization of uptake in normal organs and tumor lesions. Q J Nucl Med Mol Imaging. 2010;54:61–7.PubMedGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20:716–31.PubMedCrossRefGoogle Scholar
  13. 13.
    Lebtahi R, Le Cloirec J, Houzard C, Daou D, Sobhani I, Sassolas G, et al. Detection of neuroendocrine tumors: 99mTc-P829 scintigraphy compared with 111In-pentetreotide scintigraphy. J Nucl Med. 2002;43:889–95.PubMedGoogle Scholar
  14. 14.
    Adams S, Baum R, Rink T, Schumm-Dräger PM, Usadel KH, Hör G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med. 1998;25:79–83.PubMedCrossRefGoogle Scholar
  15. 15.
    Putzer D, Gabriel M, Kendler D, Henninger B, Knoflach M, Kroiss A, et al. Comparison of (68)Ga-DOTA-Tyr(3)-octreotide and (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography in neuroendocrine tumor patients. Q J Nucl Med Mol Imaging. 2010;54:68–75.PubMedGoogle Scholar
  16. 16.
    Middendorp M, Selkinski I, Happel C, Kranert WT, Grünwald F. Comparison of positron emission tomography with [(18)F]FDG and [(68)Ga]DOTATOC in recurrent differentiated thyroid cancer: preliminary data. Q J Nucl Med Mol Imaging. 2010;54:76–83.PubMedGoogle Scholar
  17. 17.
    Kroiss A, Putzer D, Uprimny C, Decristoforo C, Gabriel M, Santner W, et al. Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine. Eur J Nucl Med Mol Imaging. 2011;38:865–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Al-Ibraheem A, Bundschuh RA, Notni J, Buck A, Winter A, Wester HJ, et al. Focal uptake of 68Ga-DOTATOC in the pancreas: pathological or physiological correlate in patients with neuroendocrine tumours? Eur J Nucl Med Mol Imaging. 2011;38:2005–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Jacobsson H, Larsson P, Jonsson C, Jussing E, Grybäck P. Normal uptake of 68Ga-DOTA-TOC by the pancreas uncinate process mimicking malignancy at somatostatin receptor PET. Clin Nucl Med. 2012;37:362–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Miederer M, Seidl S, Buck A, Scheidhauer K, Wester HJ, Schwaiger M, et al. Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in 68Ga-DOTATOC PET/CT. Eur J Nucl Med Mol Imaging. 2009;36:48–52.PubMedCrossRefGoogle Scholar
  21. 21.
    Kabasakal L, Demirci E, Ocak M, Decristoforo C, Araman A, Ozsoy Y, et al. Comparison of (68)Ga-DOTATATE and (68)Ga-DOTANOC PET/CT imaging in the same patient group with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2012;39:1271–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med. 2004;45:1519–27.PubMedGoogle Scholar
  23. 23.
    Jaskowiak CJ, Bianco JA, Perlman SB, Fine JP. Influence of reconstruction iterations on 18F-FDG PET/CT standardized uptake values. J Nucl Med. 2005;46:424–8.PubMedGoogle Scholar
  24. 24.
    El Fakhri G, Surti S, Trott CM, Scheuermann J, Karp JS. Improvement in lesion detection with whole-body oncologic time-of-flight PET. J Nucl Med. 2011;52:347–53.PubMedCrossRefGoogle Scholar
  25. 25.
    Lois C, Jakoby BW, Long MJ, Hubner KF, Barker DW, Casey ME, et al. An assessment of the impact of incorporating time-of-flight information into clinical PET/CT imaging. J Nucl Med. 2010;51:237–45.PubMedCrossRefGoogle Scholar
  26. 26.
    Velikyan I, Sundin A, Eriksson B, Lundqvist H, Sörensen J, Bergström M, et al. In vivo binding of [68Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours – impact of peptide mass. Nucl Med Biol. 2010;37:265–75.PubMedCrossRefGoogle Scholar
  27. 27.
    Haug AR, Auernhammer CJ, Wängler B, Schmidt GP, Uebleis C, Göke B, et al. 68Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors. J Nucl Med. 2010;51:1349–56.PubMedCrossRefGoogle Scholar
  28. 28.
    Jentzen W. Experimental investigation of factors affecting the absolute recovery coefficients in iodine-124 PET lesion imaging. Phys Med Biol. 2010;55:2365–98.PubMedCrossRefGoogle Scholar
  29. 29.
    Beauregard JM, Hofman MS, Kong G, Hicks RJ. The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2012;39:50–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • A. Kroiss
    • 1
    Email author
  • D. Putzer
    • 1
  • C. Decristoforo
    • 1
  • C. Uprimny
    • 1
  • B. Warwitz
    • 1
  • B. Nilica
    • 1
  • M. Gabriel
    • 1
  • D. Kendler
    • 1
  • D. Waitz
    • 1
  • G. Widmann
    • 2
  • I. J. Virgolini
    • 1
  1. 1.Department of Nuclear MedicineInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Department of RadiologyInnsbruck Medical UniversityInnsbruckAustria

Personalised recommendations