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Erschienen in: Molecular Imaging and Biology 5/2019

22.02.2019 | Research Article

The Correlation Between [68Ga]DOTATATE PET/CT and Cell Proliferation in Patients With GEP-NENs

verfasst von: Jiangyuan Yu, Nan Li, Jie Li, Ming Lu, Jeffrey P. Leal, Huangying Tan, Hua Su, Yang Fan, Yan Zhang, Wei Zhao, Hua Zhu, Martin G. Pomper, Yun Zhou, Zhi Yang

Erschienen in: Molecular Imaging and Biology | Ausgabe 5/2019

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Abstract

Purpose

Objectives of the study are to analyze the correlation between [68Ga]DOTATATE positron emission tomography (PET)/X-ray computed tomography (CT) measurements and various biological characteristics of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), and to determine optimal cutoff value of SUVmax (standard uptake value) to differentiate neuroendocrine tumors (NETs) and neuroendocrine cancers (NECs).

Procedures

Of the GEP-NEN cases (73 males, 53 females; age 18–77 years) with pathologically proven primary and/or metastatic lesions, 126 were studied. All of the short axes of lesions were larger than 0.5 cm in order to avoid the partial volume effect. Patients fasted for 6 h before the PET/CT scans. The dose of [68Ga]DOTATATE was 100–200 MBq and the acquisition began at 1 h after injection. The lesion with the highest SUVmax in each patient was analyzed.

Results

In the total sample, the sensitivity of [68Ga]DOTATATE was 69.05 %. The sensitivities were significantly different among G1, G2, and G3 groups (72.22 %, 91.53 %, and 40.82 %, respectively; p < 0.01). The SUVmax of the G3 group was lowest. We also found that the sensitivity and SUVmax were significantly higher (p < 0.05) in patients with pancreatic NENs (Pan-NENs) than in patients with gastrointestinal NENs (Gi-NENs) and unknown primary NENs (Up-NENs). A significant negative correlation between SUVmax and Ki-67 was found (r = − 0.429, p < 0.01). Using SUVmax to differentiate neuroendocrine tumors (NETs) and neuroendocrine cancers (NECs), the area under the ROC curve (AUC) was 0.771 and the cutoff value of SUVmax was 11.25 (sensitivity 79.2 %, specificity 65.3 %). However, Pan-NENs did not show any statistical significance results in correlation and ROC analysis.

Conclusion

[68Ga]DOTATATE PET/CT results showed a negative correlation with GEP-NEN cell proliferation and were complementary to Ki-67. Pan-NENs were different from Gi-NENs and Up-NENs when compared to somatostatin receptor expression.
Literatur
1.
Zurück zum Zitat Garcia-Carbonero R, Capdevila J, Crespo-Herrero G, Diaz-Perez JA, Martinez del Prado MP, Alonso Orduna V, Sevilla-Garcia I, Villabona-Artero C, Beguiristain-Gomez A, Llanos-Munoz M, Marazuela M, Alvarez-Escola C, Castellano D, Vilar E, Jimenez-Fonseca P, Teule A, Sastre-Valera J, Benavent-Vinuelas M, Monleon A, Salazar R (2010) Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol 21:1794–1803CrossRef Garcia-Carbonero R, Capdevila J, Crespo-Herrero G, Diaz-Perez JA, Martinez del Prado MP, Alonso Orduna V, Sevilla-Garcia I, Villabona-Artero C, Beguiristain-Gomez A, Llanos-Munoz M, Marazuela M, Alvarez-Escola C, Castellano D, Vilar E, Jimenez-Fonseca P, Teule A, Sastre-Valera J, Benavent-Vinuelas M, Monleon A, Salazar R (2010) Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol 21:1794–1803CrossRef
2.
Zurück zum Zitat Rindi G, Petrone G, Inzani F (2014) The 2010 WHO classification of digestive neuroendocrine neoplasms: a critical appraisal four years after its introduction. Endocr Pathol 25:186–192CrossRef Rindi G, Petrone G, Inzani F (2014) The 2010 WHO classification of digestive neuroendocrine neoplasms: a critical appraisal four years after its introduction. Endocr Pathol 25:186–192CrossRef
3.
Zurück zum Zitat Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B (2007) TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 451:757–762CrossRef Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B (2007) TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 451:757–762CrossRef
4.
Zurück zum Zitat Yang Z, Tang LH, Klimstra DS (2011) Effect of tumor heterogeneity on the assessment of Ki67 labeling index in well-differentiated neuroendocrine tumors metastatic to the liver: implications for prognostic stratification. Am J Surg Pathol 35:853–860CrossRef Yang Z, Tang LH, Klimstra DS (2011) Effect of tumor heterogeneity on the assessment of Ki67 labeling index in well-differentiated neuroendocrine tumors metastatic to the liver: implications for prognostic stratification. Am J Surg Pathol 35:853–860CrossRef
5.
Zurück zum Zitat Adesoye T, Daleo MA, Loeffler AG et al (2015) Discordance of histologic grade between primary and metastatic neuroendocrine carcinomas. Ann Surg Oncol Suppl 3:S817–S821CrossRef Adesoye T, Daleo MA, Loeffler AG et al (2015) Discordance of histologic grade between primary and metastatic neuroendocrine carcinomas. Ann Surg Oncol Suppl 3:S817–S821CrossRef
6.
Zurück zum Zitat Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F (2008) Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 26:4311–4318CrossRef Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F (2008) Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 26:4311–4318CrossRef
7.
Zurück zum Zitat Singh S, Hallet J, Rowsell C, Law CH (2014) Variability of Ki67 labeling index in multiple neuroendocrine tumors specimens over the course of the disease. Eur J Surg Oncol 40:1517–1522CrossRef Singh S, Hallet J, Rowsell C, Law CH (2014) Variability of Ki67 labeling index in multiple neuroendocrine tumors specimens over the course of the disease. Eur J Surg Oncol 40:1517–1522CrossRef
8.
Zurück zum Zitat Campana D, Ambrosini V, Pezzilli R, Fanti S, Labate AMM, Santini D, Ceccarelli C, Nori F, Franchi R, Corinaldesi R, Tomassetti P (2010) Standardized uptake values of (68)Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors. J Nucl Med 51:353–359CrossRef Campana D, Ambrosini V, Pezzilli R, Fanti S, Labate AMM, Santini D, Ceccarelli C, Nori F, Franchi R, Corinaldesi R, Tomassetti P (2010) Standardized uptake values of (68)Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors. J Nucl Med 51:353–359CrossRef
9.
Zurück zum Zitat Tirosh A, Papadakis GZ, Millo C et al (2018) Prognostic utility of Total 68Ga-DOTATATE-avid tumor volume in patients with neuroendocrine tumors. Gastroenterology 154:998–1008CrossRef Tirosh A, Papadakis GZ, Millo C et al (2018) Prognostic utility of Total 68Ga-DOTATATE-avid tumor volume in patients with neuroendocrine tumors. Gastroenterology 154:998–1008CrossRef
10.
Zurück zum Zitat Reubi JC, Kvols L, Krenning E, Lamberts SW (1991) In vitro and in vivo detection of somatostatin receptors in human malignant tissues. Acta Oncol 30:463–468CrossRef Reubi JC, Kvols L, Krenning E, Lamberts SW (1991) In vitro and in vivo detection of somatostatin receptors in human malignant tissues. Acta Oncol 30:463–468CrossRef
11.
Zurück zum Zitat Kvols LK, Reubi JC, Horisberger U et al (1992) The presence of somatostatin receptors in malignant neuroendocrine tumor tissue predicts responsiveness to octreotide. Yale J Biol Med 65:505–518PubMedPubMedCentral Kvols LK, Reubi JC, Horisberger U et al (1992) The presence of somatostatin receptors in malignant neuroendocrine tumor tissue predicts responsiveness to octreotide. Yale J Biol Med 65:505–518PubMedPubMedCentral
12.
Zurück zum Zitat Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20CrossRef Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20CrossRef
13.
Zurück zum Zitat Gerdes J, Lemke H, Baisch H et al (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715PubMed Gerdes J, Lemke H, Baisch H et al (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715PubMed
14.
Zurück zum Zitat Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322CrossRef Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322CrossRef
15.
Zurück zum Zitat Martin B, Paesmans M, Mascaux C, Berghmans T, Lothaire P, Meert AP, Lafitte JJ, Sculier JP (2004) Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 91:2018–2025CrossRef Martin B, Paesmans M, Mascaux C, Berghmans T, Lothaire P, Meert AP, Lafitte JJ, Sculier JP (2004) Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 91:2018–2025CrossRef
16.
Zurück zum Zitat Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, Ortmann O (2013) Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat 139:539–552CrossRef Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, Ortmann O (2013) Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat 139:539–552CrossRef
17.
Zurück zum Zitat Klimstra DS (2013) Pathology reporting of neuroendocrine tumors: essential elements for accurate diagnosis, classification, and staging. Semin Oncol 40:23–36CrossRef Klimstra DS (2013) Pathology reporting of neuroendocrine tumors: essential elements for accurate diagnosis, classification, and staging. Semin Oncol 40:23–36CrossRef
18.
Zurück zum Zitat Dhall D, Mertens R, Bresee C, Parakh R, Wang HL, Li M, Dhall G, Colquhoun SD, Ines D, Chung F, Yu R, Nissen NN, Wolin E (2012) Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors. Hum Pathol 43:489–495CrossRef Dhall D, Mertens R, Bresee C, Parakh R, Wang HL, Li M, Dhall G, Colquhoun SD, Ines D, Chung F, Yu R, Nissen NN, Wolin E (2012) Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors. Hum Pathol 43:489–495CrossRef
19.
Zurück zum Zitat Miller HC, Drymousis P, Flora R, Goldin R, Spalding D, Frilling A (2014) Role of Ki-67 proliferation index in the assessment of patients with neuroendocrine neoplasias regarding the stage of disease. World J Surg 38:1353–1361CrossRef Miller HC, Drymousis P, Flora R, Goldin R, Spalding D, Frilling A (2014) Role of Ki-67 proliferation index in the assessment of patients with neuroendocrine neoplasias regarding the stage of disease. World J Surg 38:1353–1361CrossRef
20.
Zurück zum Zitat O’Toole D, Saveanu A, Couvelard A, Gunz G, Enjalbert A, Jaquet P, Ruszniewski P, Barlier A (2006) The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies. Eur J Endocrinol 155:849–857CrossRef O’Toole D, Saveanu A, Couvelard A, Gunz G, Enjalbert A, Jaquet P, Ruszniewski P, Barlier A (2006) The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies. Eur J Endocrinol 155:849–857CrossRef
Metadaten
Titel
The Correlation Between [68Ga]DOTATATE PET/CT and Cell Proliferation in Patients With GEP-NENs
verfasst von
Jiangyuan Yu
Nan Li
Jie Li
Ming Lu
Jeffrey P. Leal
Huangying Tan
Hua Su
Yang Fan
Yan Zhang
Wei Zhao
Hua Zhu
Martin G. Pomper
Yun Zhou
Zhi Yang
Publikationsdatum
22.02.2019
Verlag
Springer International Publishing
Erschienen in
Molecular Imaging and Biology / Ausgabe 5/2019
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-019-01328-3

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