Localization of Hidden Insulinomas with 68Ga-DOTA-Exendin-4 PET/CT: A Pilot Study

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FIGURE 1.
(A and B) Coronal (A) and transaxial (B) PET/CT images from patient 4 obtained 2.5 h after injection of 80 MBq of ⁶⁸Ga-DOTA-exendin-4. (C and D) Coronal (C) and transaxial (D) SPECT/CT images of same patient 72 h after injection of 90 MBq of ¹¹¹In-DOTA-exendin-4. Focal uptake of ¹¹¹In-DOTA-exendin-4 and ⁶⁸Ga-DOTA-exendin-4 is seen in pancreatic body (arrows); patient has refused surgery so far.
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FIGURE 2.
(A and B) Coronal (A) and transaxial (B) PET/CT images from patient 5 obtained 2.5 h after injection of 76 MBq of ⁶⁸Ga-DOTA-exendin-4. (C and D) Coronal (C) and transaxial (D) SPECT/CT images of same patient 72 h after injection of 66 MBq of ¹¹¹In-DOTA-exendin-4. Arrows show focal ⁶⁸Ga-DOTA-exendin-4 uptake in distal pancreatic tail consistent with surgically removed insulinoma. SPECT/CT did not show the insulinoma.
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FIGURE 3.
Hormone and receptor evaluation of resected insulinoma in patient 5. (A) Immunohistochemistry for insulin showing strongly labeled tumor cells. (B) Hematoxylin- and eosin-stained tumor tissue. (C) In vitro autoradiography revealing high GLP-1R density (mean, 5,766 dpm/mg of tissue). (D) Autoradiogram showing nonspecific binding of ¹²⁵I-GLP-1 (7–36) amide in presence of 100 nM GLP-1 (7–36) amide.

TABLE 1

Clinical Characteristics

Characteristic	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Age (y)	39	48	64	63	56
Sex	F	F	M	M	F
Presenting symptoms	Hypoglycemia, palpitation, hyperhidrosis	Hypoglycemia, dizziness, hyperhidrosis	Hypoglycemia, palpitation, hyperhidrosis	Hypoglycemia, palpitation, hyperhidrosis	Hypoglycemia, tachypnea, hyperhidrosis
Duration of symptoms (mo)	20	39	48	24	24

TABLE 2

Preoperative Imaging and Operative Procedures

Procedure	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Conventional imaging
CT	FN	NA	NA	NA	NA
ASVS	FN	FN	NA	NA	NA
Endoscopic ultrasound	FN	FN	FN	NA	NC
MR imaging	FN	FN	FN	−	TP
¹¹¹In-DOTA-exendin-4 SPECT/CT
Detection of tumor 4 h after injection	FN	TP	TP	+	FN
Tumor-to-background ratio at 4 h	NA	1.04	3.87	1.96	NA
Detection of tumor 72 h after injection	FP	TP	TP	+	FP
Tumor-to-background ratio at 72 h	NA	1.12	3.93	2.04	NA
⁶⁸Ga-DOTA-exendin-4 PET/CT
Detection of tumor	TP	TP	TP	+	TP
Tumor-to-background ratio	2.00	3.79	6.87	5.95	32.42
SUV_max of tumor	5.5	10.8	49.1	25	30.8
Surgery and histology
Surgical procedure	Enucleation	Pancreas tail resection	Pancreas tail resection	Not operated	Enucleation
Localization	Body/tail transition	Tail	Tail	NA	Tail
Dimension (mm)	8	10	10	NA	18
Histopathology	Insulinoma	Insulinoma	Insulinoma	NA	Insulinoma

ASVS = selective arterial calcium stimulation and hepatic venous sampling; SUV_max = maximal standardized uptake value; NA = not applicable; NC = not conclusive; FN = false-negative; FP = false-positive; TP = true-positive; − = negative result; + = positive result.