Advertisement

Comparison of sequential planar 177Lu-DOTA-TATE dosimetry scans with 68Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy

  • Aurora Sainz-Esteban
  • Vikas Prasad
  • Christiane Schuchardt
  • Carolin Zachert
  • José Manuel Carril
  • Richard P. Baum
Original Article

Abstract

Purpose

The aim of the study was to compare sequential 177Lu-DOTA-TATE planar scans (177Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic 68Ga-DOTA-TATE positron emission tomography (PET)/CT (68Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods.

Methods

A total of 44 patients (59 ± 11 years old) with biopsy-proven NET underwent 68Ga-DOTA-TATE and 177Lu-DOTA-TATE imaging within 7.9 ± 7.5 days between the two examinations. 177Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on 177Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on 68Ga-DOTA-TATE studies obtained before PRRT.

Results

A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were 68Ga-DOTA-TATE positive and 177Lu-DOTA-TATE negative, whereas 9 were 68Ga-DOTA-TATE negative and 177Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for 177Lu-DOTA-TATE as compared to 68Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) 177Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p < 0.05). No such significance was found for differences in maximum standardized uptake value (SUVmax). However, concordant liver lesions with a score from 1 to 3 in the 72-h 177Lu-DOTA-TATE scan had a lower SUVmax (n = 23; mean 10.9) than those metastases with a score of 4 (n = 97; mean SUVmax 18) (p < 0.05).

Conclusion

Although 177Lu-DOTA-TATE planar dosimetry scans exhibited a very good sensitivity for the detection of metastases, they failed to pick up 9% of lesions seen on the 68Ga-DOTA-TATE PET/CT. Three-dimensional dosimetry using single photon emission computed tomography/CT could be applied to investigate this issue further. Delayed (72 h) images are most suitable for drawing regions of interest for dosimetric calculations.

Keywords

177Lu-DOTA-TATE Dosimetry scan 68Ga-DOTA-TATE Neuroendocrine tumour 

Notes

Acknowledgments

The authors would like to thank the nursing and technician staff in the Bad Berka Zentralklinik for their technical assistance. We would also like to thank all supporting personnel of the radiopharmacy department for their expert help and effort. We are grateful for the support from the coworkers of the Department of Nuclear Medicine/PET Centre, Bad Berka, Germany. All of the patients included in this study were enrolled in the Department of Nuclear Medicine/PET Centre, Bad Berka, Germany. Image acquisition, patients’ therapeutic management and follow-up were also performed in the Department of Nuclear Medicine/PET Centre, Bad Berka, Germany. Aurora Sainz-Esteban performed this study during a European programme of internship abroad between the Zentralklinik Bad Berka (Bad Berka, Germany) and the Hospital Universitario Marqués de Valdecilla (Santander, Spain).

Authors’ contributions

Each author has contributed significantly to the submitted work. Aurora Sainz-Esteban contributed to the conception and design of the study, acquired, analysed and interpreted the data and wrote the manuscript. Vikas Prasad contributed to the conception and design of the study, performed the PET/CT and the dosimetry studies, analysed the data and critically revised and approved the final manuscript. Christiane Schuchardt and Carolin Zachert performed the dosimetry studies and critically read the manuscript. José Manuel Carril critically revised and approved the final manuscript. Richard Paul Baum conceived the study, performed the PET/CT and dosimetry studies and critically revised and approved the final manuscript.

Conflicts of interest

None.

References

  1. 1.
    Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 2008;9:61–72.PubMedCrossRefGoogle Scholar
  2. 2.
    Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003;24:389–427.PubMedCrossRefGoogle Scholar
  3. 3.
    Reubi JC, Schär 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
  4. 4.
    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
  5. 5.
    Prasad V, Ambrosini V, Hommann M, Hoersch D, Fanti S, Baum RP. Detection of unknown primary neuroendocrine tumours (CUP-NET) using (68)Ga-DOTA-NOC receptor PET/CT. Eur J Nucl Med Mol Imaging 2010;37:67–77.PubMedCrossRefGoogle Scholar
  6. 6.
    Sainz-Esteban A, Prasad V, Carril JM, Baum RP. Pancreatic neuroendocrine tumor with involvement of the inferior mesenteric vein diagnosed by Ga-68 DOTA-TATE PET/CT. Clin Nucl Med 2010;35:40–1.PubMedCrossRefGoogle Scholar
  7. 7.
    Srirajaskanthan R, Kayani I, Quigley AM, Soh J, Caplin ME, Bomanji J. The role of 68Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111In-DTPA-octreotide scintigraphy. J Nucl Med 2010;51:875–82.PubMedCrossRefGoogle Scholar
  8. 8.
    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
  9. 9.
    Kaemmerer D, Peter L, Lupp A, Schulz S, Sänger J, Prasad V, et al. Molecular imaging with (68)Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2011;38:1659–68.PubMedCrossRefGoogle Scholar
  10. 10.
    Forrer F, Valkema R, Kwekkeboom DJ, de Jong M, Krenning EP. Neuroendocrine tumors. Peptide receptor radionuclide therapy. Best Pract Res Clin Endocrinol Metab 2007;21:111–29.PubMedCrossRefGoogle Scholar
  11. 11.
    van Essen M, Krenning EP, Bakker WH, de Herder WW, van Aken MO, Kwekkeboom DJ. Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin. Eur J Nucl Med Mol Imaging 2007;34:1219–27.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Kwekkeboom DJ, de Herder WW, van Eijck CH, Kam BL, van Essen M, Teunissen JJ, et al. Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2010;40:78–88.PubMedCrossRefGoogle Scholar
  15. 15.
    Sowa-Staszczak A, Pach D, Chrzan R, Trofimiuk M, Stefańska A, Tomaszuk M, et al. Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs). Eur J Nucl Med Mol Imaging 2011;38:1669–74.PubMedCrossRefGoogle Scholar
  16. 16.
    Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med 2007;48:1741–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Meyer GJ, Mäcke H, Schuhmacher J, Knapp WH, Hofmann M. 68 Ga-labelled DOTA-derivatised peptide ligands. Eur J Nucl Med Mol Imaging 2004;31:1097–104.PubMedCrossRefGoogle Scholar
  18. 18.
    Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, et al. [177Lu-DOTA0Tyr3]octreotate: comparison with [111In-DTPA0]octreotide in patients. Eur J Nucl Med 2001;28:1319–25.PubMedCrossRefGoogle Scholar
  19. 19.
    Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, et al. 86Y-DOTA0-D-Phe1-Tyr3-octreotide (SMT487)—a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging 2003;30:510–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med 2006;36:228–47.PubMedCrossRefGoogle Scholar
  21. 21.
    Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer 2008;112:2447–55.PubMedCrossRefGoogle Scholar
  22. 22.
    Kayani I, Conry BG, Groves AM, Win T, Dickson J, Caplin M, et al. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. J Nucl Med 2009;50:1927–32.PubMedCrossRefGoogle Scholar
  23. 23.
    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
  24. 24.
    Wong KK, Cahill JM, Frey KA, Avram AM. Incremental value of 111-In pentetreotide SPECT/CT fusion imaging of neuroendocrine tumors. Acad Radiol 2010;17:291–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Even-Sapir E, Keidar Z, Bar-Shalom R. Hybrid imaging (SPECT/CT and PET/CT)–improving the diagnostic accuracy of functional/metabolic and anatomic imaging. Semin Nucl Med 2009;39:264–75.PubMedCrossRefGoogle Scholar
  26. 26.
    Mirzaei S, Bastati B, Lipp RW, Knoll P, Zojer N, Ludwig H. Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors. Oncology 2011;80:326–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Sandström M, Garske U, Granberg D, Sundin A, Lundqvist H. Individualized dosimetry in patients undergoing therapy with (177)Lu-DOTA-D-Phe (1)-Tyr (3)-octreotate. Eur J Nucl Med Mol Imaging 2010;37:212–25.PubMedCrossRefGoogle Scholar
  28. 28.
    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
  29. 29.
    Helisch A, Förster GJ, Reber H, Buchholz HG, Arnold R, Göke B, et al. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004;31:1386–92.PubMedCrossRefGoogle Scholar
  30. 30.
    de Araújo EB, Caldeira Filho JS, Nagamati LT, Muramoto E, Colturato MT, Couto RM, et al. A comparative study of 131I and 177Lu labeled somatostatin analogues for therapy of neuroendocrine tumours. Appl Radiat Isot 2009;67:227–33.PubMedCrossRefGoogle Scholar
  31. 31.
    Antunes P, Ginj M, Zhang H, Waser B, Baum RP, Reubi JC, et al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals? Eur J Nucl Med Mol Imaging 2007;34:982–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH, et al. Comparison of [(177)Lu-DOTA(0), Tyr(3)]octreotate and [(177)Lu-DOTA(0), Tyr(3)]octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging 2006;33:1346–51.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Aurora Sainz-Esteban
    • 1
  • Vikas Prasad
    • 2
  • Christiane Schuchardt
    • 2
  • Carolin Zachert
    • 2
  • José Manuel Carril
    • 1
  • Richard P. Baum
    • 2
  1. 1.Department of Nuclear MedicineHospital Universitario Marqués de ValdecillaSantanderSpain
  2. 2.Department of Nuclear Medicine and Centre for PET/CTZentralklinik Bad BerkaBad BerkaGermany

Personalised recommendations