Evaluation of [68Ga]Ga-DATA-TOC for imaging of neuroendocrine tumours: comparison with [68Ga]Ga-DOTA-NOC PET/CT

  • Divya Yadav
  • Sanjana Ballal
  • Madhav Prasad Yadav
  • Madhavi Tripathi
  • Frank Roesch
  • Chandrasekhar BalEmail author
Original Article
Part of the following topical collections:
  1. Oncology – Digestive tract



Recently, the new hybrid chelator DATA (6-amino-1,4-diazepine-triacetate) has been introduced, which has the advantage of high yield and radiolabelling of DATA-based octreotide derivative (TOC) at room temperature in contrast to tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) that needs 95 °C for effective labelling. However, the diagnostic potential of DATA-TOC has not been studied with other chelators in humans. The aim of this study was to compare the diagnostic efficacy of [68Ga]Ga-DATA-TOC with [68Ga]Ga-DOTA-NOC (which is the current standard for imaging neuroendocrine tumours (NET)) in patients of gastroenteropancreatic neuroendocrine tumours (GEP-NETs).


Fifty patients (thirty-one males and nineteen females) with biopsy-proven GEP-NETs were included in the study. Patients age ranged from 14 to 75 years (mean 46.11 years). All patients underwent two PET studies with [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC. Images were evaluated visually and semi-quantitatively using maximum standardized uptake values (SUVmax) of tumour, mediastinum and liver. Tumour-to-liver (T/L) and tumour-to-mediastinum (T/M) SUVmax ratios were computed. For the purpose of comparison, patient-wise as well as lesion-wise analysis was carried out. The nonparametric-related samples Wilcoxon signed-rank test was used for comparison of the SUVmax values and ratios.


On visual evaluation, the biodistribution and image quality of [68Ga]Ga-DATA-TOC was similar to [68Ga]Ga-DOTA-NOC. Physiological liver uptake was lower in [68Ga]Ga-DATA-TOC as compared with [68Ga]Ga-DOTA-NOC, 7.65 ± 5.37 vs 8.94 ± 5.95 (p = 0.009), respectively. On a patient-wise analysis, both [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC were lesion-positive in the 44 patients (88%) and were negative in the 6 patients (12%). On a lesion-based analysis, [68Ga]Ga-DATA-TOC had 98.6% concordance with [68Ga]Ga-DOTA-NOC (232 out of 235 lesions detected). The target tumour SUVmax on [68Ga]Ga-DATA-TOC and [68Ga]Ga-DOTA-NOC were 36.63 ± 32.24 and 40.82 ± 36.89, respectively (p = 0.097). The T/L SUVmax ratios were not significantly different (5.99 ± 5.52 vs 5.67 ± 4.96, p = 0.77).


[68Ga]Ga-DATA-TOC PET/CT imaging produced results that were comparable with [68Ga]Ga-DOTA-NOC. It, thus, has potential utility as an effective and safe alternative to 68Ga-DOTA-NOC with the added benefit of ease, cost-effective and improved yield of instant kit-type synthesis.


Neuroendocrine tumours Somatostatin receptor imaging PET/CT 68Ga-DATA-TOC 68Ga-DOTA-NOC 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical clearance

Received from Institute Ethics Committee (Ref. No. IECPG-101/30.12.2015).

Informed consent

Informed consent was obtained from all patients.


This work has not been submitted elsewhere or has not under consideration to any other journal.


  1. 1.
    Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3(10):1335–42.CrossRefGoogle Scholar
  2. 2.
    National Cancer Institute. Surveillance, Epidemiology, and End Results Program.
  3. 3.
    Rindi G, Arnold R, Bosman FT. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: WHO Classification of Tumours of the Digestive System (4th Edition). International Agency for Research on Cancer (IARC); 2010; France, 13–14.Google Scholar
  4. 4.
    Kumar R, Sharma P, Garg P, Karunanithi S, Naswa N, Sharma R, et al. Role of (68)Ga-DOTATOC PET-CT in the diagnosis and staging of pancreatic neuroendocrine tumours. Eur Radiol. 2011;21:2408–14.CrossRefGoogle Scholar
  5. 5.
    Jain TK, Karunanithi S, Dhull VS, Roy SG, Kumar R. Carcinoma of unknown primary of neuroendocrine origin: accurate detection of primary with (68)Ga-labelled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI3-octreotide positron emission tomography/computed tomography enterography. Indian J Nucl Med. 2014;29(2):122–3.CrossRefGoogle Scholar
  6. 6.
    Hicks RJ, Kwekkeboom DJ, Krenning E, Bodei L, Grozinsky-Glasberg S, Arnold R, et al. ENETS consensus guidelines for the standards of care in neuroendocrine neoplasia: peptide receptor radionuclide therapy with radiolabelled somatostatin analogues. Neuroendocrinology. 2017;105:295–309.CrossRefGoogle Scholar
  7. 7.
    Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of 177Lu-DOTATE for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125–35.CrossRefGoogle Scholar
  8. 8.
    Spang P, Herrmann C, Roesch F. Bifunctional gallium-68 chelators: past, present, and future. Semin Nucl Med. 2016;46(5):373–94.CrossRefGoogle Scholar
  9. 9.
    Waldron BP, Parker D, Burchardt C, Yufit DS, Zimny M, Roesch F, et al. Structure and stability of hexadentate complexes of ligands based on AAZTA for efficient PET labelling with gallium-68. Chem Commun (Camb). 2013;49(6):579–81.CrossRefGoogle Scholar
  10. 10.
    Seemann J, Eppard E, Waldron BP, Ross TL, Roesch F. Cation exchange-based post-processing of 68Ga-eluate: a comparison of three solvent systems for labelling of DOTATOC, NO2AP(BP) and DATA(m). Appl Radiat Isot. 2015;98:54–9.CrossRefGoogle Scholar
  11. 11.
    Farkas E, Nagel J, Waldron BP, Parker D, Tóth I, Brücher E, et al. Equilibrium, kinetic and structural properties of gallium(III) and some divalent metal complexes formed with the new DATAm and DATA5m ligands. Chem Eur J. 2017;23(43):10358–71.CrossRefGoogle Scholar
  12. 12.
    Sinnes J-P, Nagel J, Waldron B, Maina T, Nock BA, Bergmann RK, et al. Instant kit-preparation of 68Ga-radiopharmaceuticals via the chimeric chelator DATA: proof-of-principle with [68Ga]Ga-DATA-TOC. EJNMMI Res. 2019;9(1):48.CrossRefGoogle Scholar
  13. 13.
    Seemann J, Waldron BP, Roesch F, Parker D. Approaching ‘kit-type’ labelling with 68Ga: the DATA chelators. ChemMedChem. 2015;10:1019–26.CrossRefGoogle Scholar
  14. 14.
    Seemann J, Waldron BP, Parker D, Roesch F. DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature. EJNMMI Radiopharmacy Chem. 2016;1:4.CrossRefGoogle Scholar
  15. 15.
    Nock AB, Kaloudi A, Nagel J, Sinnes JP, Roesch F, Theodosia MT. Novel bifunctional DATA chelator for quick access to site-directed PET 68Ga-radiotracers: preclinical proof-of-principle with [Tyr3] octreotide. Dalton Trans. 2017;46:14584–90.CrossRefGoogle Scholar
  16. 16.
    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
  17. 17.
    Schmidt-Kreppel B, Plum T, Gaertner FC, Maina T, Nock BA, Bergmann RK, et al. Biodistribution of [68Ga]Ga-DATA-TOC in comparison with [68Ga]Ga-DOTATOC in normal tissues and neuroendocrine tumour lesions. Eur J Nucl Med Mol Imaging. 2017;44(2):119–956.Google Scholar
  18. 18.
    Johnbeck CB, Knigge U, Kjær A. PET tracers for somatostatin receptor imaging of neuroendocrine tumors: current status and review of the literature. Future Oncol. 2014;10(14):2259–77.CrossRefGoogle Scholar
  19. 19.
    Bodei L, Ambrosini V, Herrmann K, Modlin I, et al. Current concepts in 68GA-DOTATATE NEN imaging: interpretation, biodistribution, dosimetry and molecular strategies. J Nucl Med. 2017;58(11):1718–26.CrossRefGoogle Scholar
  20. 20.
    Ambrosini V, Campana D, Tomassetti P, Grassetto G, Rubello D, Fanti S. PET/CT with 68Gallium-DOTA-peptides in NET: an overview. Eur J Radiol. 2011;80(2):116–9.CrossRefGoogle Scholar
  21. 21.
    Wild D, Bomanji JB, Benkert P, Maecke H, Ell PJ, Reubi JC, et al. Comparison of [68Ga]Ga-DOTA-NOC and 68Ga-DOTATATE PET/CT within patients with gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2013;54(3):364–72.CrossRefGoogle Scholar
  22. 22.
    Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V. Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine. 2012;42(1):80–7.CrossRefGoogle Scholar
  23. 23.
    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.CrossRefGoogle Scholar
  24. 24.
    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.CrossRefGoogle Scholar
  25. 25.
    Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W. Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol. 2010;55:389–98.CrossRefGoogle Scholar
  26. 26.
    Breeman WA, de Blois E, Sze Chan H, Konijnenberg M, Kwekkeboom DJ, Krenning EP. 68Ga-labeled DOTA-peptides and 68Ga-labeled radiopharmaceuticals for positron emission tomography: current status of research, clinical applications, and future perspectives. Semin Nucl Med. 2011;41:314–21.CrossRefGoogle Scholar
  27. 27.
    Frilling A, Sotiropoulos GC, Radtke A, Malago M, Bockisch A, Kuehl H, et al. The impact of 68Ga-DOTATOC positron emission tomography/computed tomography on the multimodal management of patients with neuroendocrine tumors. Ann Surg. 2010;252:850–6.CrossRefGoogle Scholar
  28. 28.
    Ambrosini V, Campana D, Bodei L, Nanni C, Castellucci P, Allegri V, et al. [68Ga]Ga-DOTA-NOCPET/CT clinical impact in patients with neuroendocrine tumors. J Nucl Med. 2010;51:669–73.CrossRefGoogle Scholar
  29. 29.
    Naswa N, Sharma P, Kumar A, Nazar AH, Kumar R, Chumber S, et al. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. AJR Am J Roentgenol. 2011;197:1221–8.CrossRefGoogle Scholar
  30. 30.
    Waldron B, Roesch F, Parker D. Novel chelators for 68-Gallium PET. J Nucl Med. 2013;54(2):497–507.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Nuclear MedicineAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Institute of Nuclear ChemistryJohannes Gutenberg University MainzMainzGermany

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