Tailored imaging of islet cell tumors of the pancreas amidst increasing options  Helle-Brit Fiebrich, Sophie J. van Asselt, Adrienne H. Brouwers, Hendrik M. van Dullemen, Milan E.J. Pijl, Philip H. Elsinga, Thera P. Links, Elisabeth G.E. de Vries  Critical Reviews in Oncology / Hematology  Volume 82, Issue 2, Pages 213-226 (May 2012) DOI: 10.1016/j.critrevonc.2011.05.006 Copyright © 2011 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 Results of endoscopic ultrasound presented in a Forest plot analysis. On the left side of this plot the reference of the study is mentioned, on the right side sensitivities from literature data are provided with their calculated confidence intervals and number of patients. Results are clustered per imaging indication. Within the different groups studies are clustered per tumor subtype and according to year of publishing. 95% CI: 95% Confidence Interval. Critical Reviews in Oncology / Hematology 2012 82, 213-226DOI: (10.1016/j.critrevonc.2011.05.006) Copyright © 2011 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 Patient with a small, 0.6×0.9cm, metastasized glucagonoma, presenting with diabetes mellitus, jaundice and a rash. (A) Endoscopic ultrasound, showing the pancreatic tumor (arrow). On the left adjacent to the tumor the splenic artery (s.a.) and the hepatocaval confluence (c) are visible. (B) The lesion is not visualized by computer tomography. Critical Reviews in Oncology / Hematology 2012 82, 213-226DOI: (10.1016/j.critrevonc.2011.05.006) Copyright © 2011 Elsevier Ireland Ltd Terms and Conditions

Fig. 3 Illustration of yield of different imaging techniques in a patient with a metastasized non-functioning islet cell tumor, 2×2.7cm. A lesion in the pancreas and liver metastases are visualized on all imaging techniques. (A) Computer tomography shows precise anatomical location of the pancreatic lesion and of multiple liver metastases. (B) Somatostatin receptor scintigraphy shows tracer uptake in pancreas and liver lesions. (C) 11C-HTP PET demonstrates uptake in the pancreas and multiple liver metastases. (D) 18F-DOPA PET shows lesions in the pancreas and liver, more lesions were observed with 11C-HTP PET. (E) A fusion image of 11C-HTP PET and CT demonstrates multiple liver metastases. Critical Reviews in Oncology / Hematology 2012 82, 213-226DOI: (10.1016/j.critrevonc.2011.05.006) Copyright © 2011 Elsevier Ireland Ltd Terms and Conditions

Fig. 4 Results of computer tomography in publications published between 2003 and January 2010 and all MDCT studies presented in a Forest plot analysis. On the left side of this plot the reference of the study is mentioned, on the right side sensitivities from literature data are provided with their calculated confidence intervals and number of patients. Results are clustered per imaging indication. Within the different groups studies are clustered per tumor subtype and according to year of publishing. 95% CI: 95% Confidence Interval. Critical Reviews in Oncology / Hematology 2012 82, 213-226DOI: (10.1016/j.critrevonc.2011.05.006) Copyright © 2011 Elsevier Ireland Ltd Terms and Conditions

Fig. 5 Results of magnetic resonance imaging presented in a Forest plot analysis. On the left side of this plot the reference of the study is mentioned, on the right side sensitivities from literature data are provided with their calculated confidence intervals and number of patients. Results are clustered per imaging indication. Within the different groups studies are clustered per tumor subtype and according to year of publishing. 95% CI: 95% Confidence Interval. Critical Reviews in Oncology / Hematology 2012 82, 213-226DOI: (10.1016/j.critrevonc.2011.05.006) Copyright © 2011 Elsevier Ireland Ltd Terms and Conditions

Fig. 6 Schematic depiction of the different metabolic pathways by which neuroendocrine tumors can be visualized using nuclear medicine imaging techniques. This can be receptor based techniques and techniques which use the metabolic properties of these tumors. 11C-5-HTP: 11C-5-hydroxytryptophan, 18F-DOPA: 18F-fluoro-dihydroxyphenylalanin, 18F-FDG: 18F-fluoro-2-deoxy-d-glucose, 18F-FDG-6-P: 18F-fluoro-2-deoxy-d-glucose-6-phosphate, GLP-1: glucagon-like peptide 1, LAT: large amino acid transporter, VMAT: vesicular monoamine transporter. Critical Reviews in Oncology / Hematology 2012 82, 213-226DOI: (10.1016/j.critrevonc.2011.05.006) Copyright © 2011 Elsevier Ireland Ltd Terms and Conditions

Fig. 7 Results of somatostatin receptor scintigraphy presented in a Forest plot analysis. On the left side of this plot the reference of the study is mentioned, on the right side sensitivities from literature data are provided with their calculated confidence intervals and number of patients. Results are clustered per imaging indication. Within the different groups studies are clustered per tumor subtype and according to year of publishing. 95% CI: 95% Confidence Interval. Critical Reviews in Oncology / Hematology 2012 82, 213-226DOI: (10.1016/j.critrevonc.2011.05.006) Copyright © 2011 Elsevier Ireland Ltd Terms and Conditions