Article Figures & Data
Figures
- FIGURE 1.
Example of GLP-1 receptor–positive and sst2 receptor–negative malignant insulinoma (patient 2). GLP-1 receptor scintigraphy (A) and SPECT/CT (B) were performed 4 h after injection of 111In-DTPA-exendin-4 (109 MBq), and sst2 receptor PET/CT (E and F) was performed 1 h after injection of 68Ga-DOTATATE (149 MBq). Tumor tissue samples from same patient were used for in vitro GLP-1 (C and D) and sst2 receptor (G and H) quantification. There is focal 111In-DTPA-exendin-4 uptake in 2 liver lesions, 1 cardiophrenic lesion, 1 left retroclavicular lymph node, and 1 retrosternal lymph node (A). Moreover, dotted circle in A and arrows in B show 2 large 111In-DTPA-exendin-4–avid lymph nodes adjacent to stomach. sst2 receptor whole-body PET (E) shows normal 68Ga-DOTATATE distribution even in large lymph nodes adjacent to stomach (arrows, F). There is excellent correlation between peptide receptor imaging and in vitro receptor quantification: autoradiograms show strongly positive specific binding of 125I-GLP-1 (7-36) amide in whole tumor (C), whereas 125I-[Tyr3]-octreotide shows only nonspecific binding (G). Autoradiograms show nonspecific binding of 125I-GLP-1 (7-36) amide (D) and 125I-[Tyr3]-octreotide (H) in presence of 100 nM GLP-1 (7-36) amide and 100 nM octreotide, respectively. Bar = 1 mm.
- FIGURE 2.
Example of GLP-1 receptor–negative and sst2 receptor–positive malignant insulinoma (patient 6). Baseline GLP-1 receptor (A) and sst2 receptor scintigraphy (B) were performed 4 h after injection of 111In-DTPA-exendin-4 (124 MBq) and 99mTc-tektrotyd (669 MBq), and posttreatment sst2 receptor PET (C) was performed 1 h after injection of 68Ga-DOTATATE (165 MBq). Tumor tissue samples from same patient were used for in vitro GLP-1 (D and E) and sst2 receptor (F and G) quantification. sst2 receptor scintigraphy shows intense 99mTc-tektrotyd uptake in tail of pancreas and in multiple liver lesions (B). Arrow shows large 99mTc-tektrotyd–avid lesion in right liver lobe (B). GLP-1 receptor whole-body scan shows normal 111In-DTPA-exendin-4 distribution, even in large liver lesion (A). After distal pancreatectomy, right hemihepatectomy, and PRRT good partial remission was achieved, with residual disease in only 2 liver lesions, with maximal diameter of 1.3 cm (arrow, C). Correlation is excellent between peptide receptor imaging and in vitro receptor quantification: autoradiograms show strongly positive specific binding of 125I-[Tyr3]-octreotide in whole tumor (F), whereas 125I-GLP-1 (7–36) amide shows only nonspecific binding (D). Autoradiograms show nonspecific binding of 125I-GLP-1 (7-36) amide (E) and 125I-[Tyr3]-octreotide (G) in presence of 100 nM GLP-1 (7-36) amide and 100 nM octreotide, respectively. Bar = 1 mm.
Tables
- TABLE 1
Clinical Characteristics and Biochemical Evaluation of 11 Patients with Hypoglycemic Episodes and CT Findings Suggesting Malignant Insulinoma
Clinical characteristic Biochemical evaluation at end-of-fasting test* Clinical course after imaging Patient no. Age (y) Sex First symptoms (mo†) Duration of fasting (h) Glucose (mmol/L) C-peptide (nmol/L) Insulin (mU/L) Treatment after imaging Remission‡ status 1 62 M 1 20 1.9 0.44 3.0 TE Complete response 2 72 M 36 72 2.6 1.1 16 DS Partial response 3 54 F 24 72 1.4 2.1 31 PRRT Partial response 4 48 F 36 72 1.9 0.83 78 PRRT Persistent disease 5 53 M 6 14 1.8 2.0 143 TE Complete response 6 66 F 5 Not done Not done Not done Not done DP + DS + PRRT Partial response 7 74 M 1 72 2.3 0.43 7.0 none Persistent disease 8 68 M 9 Not done Not done Not done Not done TE + Chemotherapy Persistent disease 9 68 M 8 10 1.6 6.0 34.9 TE Persistent disease 10 78 F 1 12 2.5 3.3 80 TE Not available§ 11 55 M 3 4 2.3 0.79 20 DP Complete response ↵* In 9 of 11 patients, fasting test was performed. Patient 6 presented with confusion and unconsciousness due to hypoglycemia; fasting test was not performed, but CT scans revealed liver lesions suggestive of malignancy.
↵† Eight patients (1, 5, 6, 7, 8, 9, 10, and 11) who had neuroglycopenic symptoms less than 10 mo before recruitment did not receive specific medical therapy. Remaining 3 patients had neuroglycopenic symptoms for 24–36 mo before recruitment. They were treated individually with surgery, diazoxide, somatostatin analogs, and PRRT.
↵‡ Remission status at termination of study.
↵§ Multimorbid patient who died of liver failure shortly after surgery.
TE = tumor enucleation or whipple surgery; DS = debulking surgery; DP = distal pancreatectomy.
- TABLE 2
Comparison of Imaging Results, Receptor Autoradiography Results, and Immunohistochemical Results
In vivo imaging In vitro characteristics of tumor tissue GLP-1 receptor scan Receptor autoradiography Immunohistochemistry Patient no. CT abdomen scan, result Scan results Change of blood glucose*(mmol/L) sst2 receptor scan results GLP-1 receptor density† (dpm/mg) sst2 receptor density† (dpm/mg) Expression of additional sst receptors Insulin staining Ki67 staining 1 Positive‡ Positive 2.9/1.8 Not done 8,421 ± 645 >10,000 sst5 Positive <1% 2 Positive Positive 5.2/2.6 Negative 8,595 ± 429 Negative sst1 Positive focal 15% 3 Positive Negative 3.7/3.1 Positive Not done Not done Not done Positive focal 7% 4 Positive Negative 9.3/6.7§ Positive Not done Not done Not done Positive focal 1% 5 Positive Negative 3.7/3.2 Not done Negative >10,000 Negative Positive focal 1% 6 Positive Negative 5.6/5.0 Positive Negative >10,000 Negative Positive focal 5% 7 Positive Positive 4.9/2.0 Negative Not done Not done Not done Positive focal 1%–2% 8 Positive║ Not done Not done Not done Negative 978 ± 241 sst1 Positive 1% 9 Positive¶ Not done Not done Not done Negative >10,000 Negative Positive 2% 10 Positive Positive 5.3/2.0 Negative Not done Not done Not done Positive Not done 11 Positive Not done Not done Not done Negative >10,000 Negative Positive 3% ↵* Blood sugar level before injection and blood glucose nadir after injection of 111In-DTPA-exendin-4.
↵† Receptor density (dpm/mg of tissue; mean ± SEM, n = 3).
↵‡ Insulinoma in pancreas was missed by CT.
↵§ Diabetic patient.
↵║ Ultrasound.
↵¶ MRI.
Diagnosis of malignant insulinoma was confirmed in all patients by receptor imaging or receptor autoradiography and immunohistochemistry.
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