SUV of [68Ga]DOTATOC-PET/CT Predicts Response Probability of PRRT in Neuroendocrine Tumors - Molecular Imaging and Biology

Purpose

The goal of our study was to quantify the expression of the somatostatin receptors (SSTR2) using the maximum standardized uptake value (SUVmax) of [⁶⁸Ga]DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC) positron emission tomography (PET)-computed tomography (CT) in liver metastases of patients with neuroendocrine tumors (NETs) prior to peptide receptor radiation therapy (PRRT) and compare the initial tumor uptake with the final treatment outcome.

Procedures

SSTR2 expression of the 60 liver metastases in 30 NET patients was assessed at baseline and after PRRT by measuring SUVmax, tumor to spleen ratio (T/S ratio), and tumor to liver ratio (T/L ratio). Based on morphological changes and tumor size measured at baseline and follow-up contrast-enhanced CT (after three cycles of PRRT), lesions were divided into two groups by the following: (i) responding (n = 40) and (ii) non-responding (n = 20).

Results

Statistically significant differences were observed in the mean SUVmax for non-responding vs. responding lesions at baseline (18.00 ± 3.59 vs. 33.55 ± 4.62, p < 0.05) and for the mean T/S ratio (1.20 ± 0.37 vs. 1.90 ± 0.45, p < 0.05) and the mean T/L ratio (3.15 ± 0.53 vs. 4.97 ± 0.62, p < 0.05). Using the receiver operating characteristic curves, SUVmax was found a better metric than both T/L ratio and T/S ratio (area under the curve (AUC) of SUVmax 0.87; T/L ratio 0.78; T/S ratio 0.73) as a stratification criterion. Using a threshold value of >16.4 for SUVmax, the sensitivity and specificity in predicting responding lesions were 95 and 60 %, respectively.

Conclusion

We propose a SUVmax cutoff of >16.4 from [⁶⁸Ga]DOTATOC-PET-CT to select patients for PRRT. A T/L ratio >2.2 might present a scanner-independent criterion that enables the translation of our results to other institutions. However, the robustness of this arbitrary unit still needs to be evaluated with different PET scanners.

1. Rinke A, Muller HH, Brittinger CS et al (2009) Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27:4656–4663

   Article  CAS  PubMed  Google Scholar 

2. Modlin IM, Oberg K, Chung DC et al (2008) Gastroeneteropancreatic neuroendocrine tumors. Lancet Oncol 9:61–72

   Article  CAS  PubMed  Google Scholar 

3. Strosberg JR, Fine RL, Choi J et al (2011) First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine tumors. Cancer 117:268–275

   Article  CAS  PubMed  Google Scholar 

4. Yao JC, Shah MH, Ito T et al (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364:514–523

   Article  PubMed Central  CAS  PubMed  Google Scholar 

5. Raymond E, Dahan L, Raoul JL et al (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364:501–513

   Article  CAS  PubMed  Google Scholar 

6. Van Essen M, Krenning EP, De Jong M et al (2007) Peptide receptor radionuclide therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol 46:723–734

   Article  PubMed  Google Scholar 

7. Kwekkeboom DJ, Teunissen JJ, Bakker WH et al (2005) Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3] octreotate in patients with endocrine gastropancreatic tumors. J Clin Oncol 23:2754–2762

   Article  CAS  PubMed  Google Scholar 

8. Gabriel M, Oberauer A, Dobroyemsky G et al (2009) ⁶⁸Ga-DOTA-Tyr3-octreotide PET for assessing response to somatostatin- receptor–mediated radionuclide therapy. J Nucl Med 50:1427–1434

   Article  CAS  PubMed  Google Scholar 

9. Miederer M, Seidl S, Buck A et al (2009) Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in 68Ga-DOTATOC PET/CT. Eur J Nucl Med Mol Imaging 36:48–52

   Article  CAS  PubMed  Google Scholar 

10. Оtte A, Mueller-Brand J, Dellas S et al (1998) Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet 351:417–418

    Article  Google Scholar 

11. Giesel FL, Kratochwil C, Mehndiratta A et al (2012) Comparison of neuroendocrine tumor detection and characterization using DOTATOC-PET in correlation with contrast enhanced CT and delayed contrast enhanced MRI. Eur J Radiol 81:2820–2825

    Article  CAS  PubMed  Google Scholar 

12. Kwekkeboom DJ, de Herder WW, Kam BL et al (2008) Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3] octreotate: toxicity, efficacy, and survival. J Clin Oncol 26:2124–2130

    Article  CAS  PubMed  Google Scholar 

13. Campana D, Ambrosini V, Pezzilli R et al (2010) Standardized uptake values of 68Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors. J Nucl Med 51:353–359

    Article  PubMed  Google Scholar 

14. Koukouraki S, Strauss LG, Georgoulias V et al (2006) Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging 33:460–466

    Article  CAS  PubMed  Google Scholar 

15. Pfeifer AK, Gregersen T, Grønbæk H et al (2011) Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland. Neuroendocrinology 93:189–196

    Article  CAS  PubMed  Google Scholar 

16. Haug A, Auernhammer CJ, Wängler B (2009) Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 36:765–770

    Article  CAS  PubMed  Google Scholar 

Download references

Authors and Affiliations

1. Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany

   C. Kratochwil, M. Stefanova, E. Mavriopoulou, A. Afshar-Oromieh, W. Mier, U. Haberkorn & F. L. Giesel

2. Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany

   T. Holland-Letz

3. KKE Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany

   A. Dimitrakopoulou-Strauss

Corresponding author

Correspondence to F. L. Giesel.