Abstract
Purpose: Abundant expression of somatostatin receptors (sst) is a characteristic of neuroendocrine tumors (NET). Thus, radiolabeled somatostatin analogs have emerged as important tools for both in vivo diagnosis and therapy of NET. The two compounds most often used in functional imaging with positron emission tomography (PET) are 68Ga-DOTATATE and 68Ga-DOTATOC. Both analogs share a quite similar sst binding profile. However, the in vitro affinity of 68Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately tenfold higher than that of 68Ga-DOTATOC. This difference may affect their efficiency in detection of NET lesions, as sst2 is the predominant receptor subtype on gastroenteropancreatic NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs (68Ga-DOTATATE and 68Ga-DOTATOC) in the same patients with gastroenteropancreatic NET. Patients and Methods: Twenty-seven patients with metastatic gastroenteropancreatic NET underwent 68Ga-DOTATOC and 68Ga-DOTATATE PET/CT as part of the workup before prospective peptide receptor radionuclide therapy (PRRT). The performance of both imaging methods was analyzed and compared for detection of individual lesions per patient and for eight defined body regions. A region was regarded as positive if at least one lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUVmax) was compared for concordant lesions and renal parenchyma. Results: Fifty-one regions were found positive with both 68Ga-DOTATATE and 68Ga-DOTATOC. Overall, however, significantly fewer lesions were detected with 68Ga-DOTATATE in comparison with 68Ga-DOTATOC (174 versus 179, p < 0.05). Mean 68Ga-DOTATATE SUVmax across all lesions was significantly lower compared with 68Ga-DOTATOC (16.9 ± 6.8 versus 22.1 ± 12.0, p < 0.01). Mean SUVmax for renal parenchyma was not significantly different between 68Ga-DOTATATE and 68Ga-DOTATOC (12.6 ± 2.6 versus 12.6 ± 2.7). Conclusions: 68Ga-DOTATOC and 68Ga-DOTATATE possess similar diagnostic accuracy for detection of gastroenteropancreatic NET lesions (with a potential advantage of 68Ga-DOTATOC) despite their evident difference in affinity for sst2. Quite unexpectedly, maximal uptake of 68Ga-DOTATOC tended to be higher than its 68Ga-DOTATATE counterpart. However, tumor uptake shows high inter- and intraindividual variance with unpredictable preference of one radiopeptide. Thus, our data encourage the application of different sst ligands to enable personalized imaging and therapy of gastroenteropancreatic NET with optimal targeting of tumor receptors.
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References
Antoch G, Freudenberg LS, Stattaus J, Jentzen W, Mueller SP, Debatin JF et al (2002) Whole-body positron emission tomography-CT: optimized CT using oral and IV contrast materials. AJR Am J Roentgenol 179:1555–1560
Antoch G, Kuehl H, Kanja J, Lauenstein TC, Schneemann H, Hauth E et al (2004) Dual-modality PET/CT scanning with negative oral contrast agent to avoid artifacts: introduction and evaluation. Radiology 230:879–885. doi:10.1148/radiol.2303021287
Binderup T, Knigge U, Loft A, Mortensen J, Pfeifer A, Federspiel B et al (2010) Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med 51:704–712. doi:10.2967/jnumed.109.069765
Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M et al (2008) Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 35:1847–1856. doi:10.1007/s00259-008-0778-1
Boy C, Heusner TA, Poeppel TD, Redmann-Bischofs A, Unger N, Jentzen W et al (2011) (68)Ga-DOTATOC PET/CT and somatostatin receptor (sst1–sst5) expression in normal human tissue: correlation of sst2 mRNA and SUV(max). Eur J Nucl Med Mol Imaging. doi:10.1007/s00259-011-1760-x
Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schafer M et al (2007) Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 34:1617–1626. doi:10.1007/s00259-007-0450-1
de Jong M, Breeman WA, Bakker WH, Kooij PP, Bernard BF, Hofland LJ et al (1998) Comparison of (111)In-labeled somatostatin analogues for tumor scintigraphy and radionuclide therapy. Cancer Res 58:437–441
de Jong M, Breeman WA, Bernard BF, van Gameren A, de Bruin E, Bakker WH et al (1999) Tumour uptake of the radiolabelled somatostatin analogue [DOTA0, TYR3]octreotide is dependent on the peptide amount. Eur J Nucl Med 26:693–698
Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH et al (2006) 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 33:1346–1351. doi:10.1007/s00259-006-0172-9
Forrer F, Uusijarvi H, Waldherr C, Cremonesi M, Bernhardt P, Mueller-Brand J et al (2004) A comparison of (111)In-DOTATOC and (111)In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 31:1257–1262. doi:10.1007/s00259-004-1553-6
Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C et al (2007) 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 48:508–518.
Hoyer D, Bell GI, Berelowitz M, Epelbaum J, Feniuk W, Humphrey PP et al (1995) Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci 16:86–88. doi:S0165614700889889
Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T et al (2008) Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1, Tyr3-octreotate) and 18F-FDG. Cancer 112:2447–2455. doi:10.1002/cncr.23469
Koopmans KP, Neels ON, Kema IP, Elsinga PH, Links TP, de Vries EG et al (2009) Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results. Crit Rev Oncol Hematol 71:199–213. doi:10.1016/j.critrevonc.2009.02.009
Koukouraki S, Strauss LG, Georgoulias V, Schuhmacher J, Haberkorn U, Karkavitsas N 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. doi:10.1007/s00259-005-0006-1
Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL et al (2001) [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients. Eur J Nucl Med 28:1319–1325
Plockinger U, Rindi G, Arnold R, Eriksson B, Krenning EP, de Herder WW et al (2004) Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European neuroendocrine tumour society (ENETS). Neuroendocrinology 80: 394–424. doi: 10.1159/000085237
Poeppel TD, Binse I, Petersenn S, Lahner H, Schott M, Antoch G et al (2011) 68Ga-DOTATOC vs. 68Ga-DOTATATE PET/CT in functional imaging of Neuroendocrine Tumours. J Nucl Med 52:1864–1870
Reubi JC, Waser B (2003) Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging 30:781–793. doi:10.1007/s00259-003-1184-3
Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS et al (2000) Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 27:273–282
Reubi JC, Waser B, Schaer JC, Laissue JA (2001) Somatostatin receptor sst1–sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med 28:836–846
Rodrigues M, Traub-Weidinger T, Li S, Ibi B, Virgolini I (2006) Comparison of 111In-DOTA-DPhe1-Tyr3-octreotide and 111In-DOTA-lanreotide scintigraphy and dosimetry in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 33:532–540. doi:10.1007/s00259-005-0020-3
Rolleman EJ, Melis M, Valkema R, Boerman OC, Krenning EP, de Jong M (2010) Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues. Eur J Nucl Med Mol Imaging 37:1018–1031. doi:10.1007/s00259-009-1282-y
Storch D, Behe M, Walter MA, Chen J, Powell P, Mikolajczak R et al (2005) Evaluation of [99mTc/EDDA/HYNIC0]octreotide derivatives compared with [111In-DOTA0, Tyr3, Thr8]octreotide and [111In-DTPA0]octreotide: does tumor or pancreas uptake correlate with the rate of internalization? J Nucl Med 46:1561–1569
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216
Valkema R, Pauwels SA, Kvols LK, Kwekkeboom DJ, Jamar F, de Jong M et al (2005) Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0), Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate. J Nucl Med 46(Suppl 1):83S–91S
Velikyan I, Sundin A, Eriksson B, Lundqvist H, Sorensen J, Bergstrom M et al (2010) In vivo binding of [68Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours–impact of peptide mass. Nucl Med Biol 37:265–275. doi:10.1016/j.nucmedbio.2009.11.008
Wild D, Macke HR, Waser B, Reubi JC, Ginj M, Rasch H et al (2005) 68Ga-DOTANOC: a first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5. Eur J Nucl Med Mol Imaging 32:724. doi:10.1007/s00259-004-1697-4
Yau YY, Chan WS, Tam YM, Vernon P, Wong S, Coel M et al (2005) Application of intravenous contrast in PET/CT: does it really introduce significant attenuation correction error? J Nucl Med 46:283–291
Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA et al (2007) Processing of generator-produced 68Ga for medical application. J Nucl Med 48:1741–1748. doi:10.2967/jnumed.107.040378
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Poeppel, T.D. et al. (2013). Differential Uptake of 68Ga-DOTATOC and 68Ga-DOTATATE in PET/CT of Gastroenteropancreatic Neuroendocrine Tumors. In: Baum, R., Rösch, F. (eds) Theranostics, Gallium-68, and Other Radionuclides. Recent Results in Cancer Research, vol 194. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27994-2_18
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