Abstract
Insulinomas are the most common cause of hypoglycemia, resulting from endogenous hyperinsulinism. The diagnosis of insulinoma is established by demonstrating inappropriately high serum insulin concentrations during a spontaneous or induced episode of hypoglycemia. Most insulinomas are islet-cell tumors. They are often small (<2 cm), benign, and difficult to localize with current imaging techniques. Insulinomas can be detected using either noninvasive procedures (e.g., transabdominal ultrasonography, spiral CT, MRI, 111In-pentetreotide imaging, and 18F-l-dihydroxyphenylalanine PET) or invasive procedures (e.g., endoscopic ultrasonography) or a selective arterial calcium stimulation test with hepatic venous sampling. Methods: We performed 68Ga-DOTATATE PET/CT on 3 patients with insulinoma. Results: All patients' insulinomas were shown clearly with 68Ga-DOTATATE PET/CT. Conclusion: 68Ga-DOTATATE PET/CT imaging may be a useful noninvasive imaging technique to localize insulinomas preoperatively.
The common clinical manifestations of insulinoma are fasting hypoglycemia and neuroglycopenic symptoms. The diagnosis of insulinoma is established by demonstrating inappropriately high serum insulin concentrations during a spontaneous or induced episode of hypoglycemia (72-h fast). Virtually all insulinomas are islet-cell tumors; after biochemical diagnosis, imaging techniques are used to localize the tumor. Accurate preoperative localization of an insulinoma is desirable because some tumors may not be palpable at the time of surgery (1). The noninvasive procedures available include transabdominal ultrasonography, spiral CT, MRI, 111In-pentetreotide imaging, and 18F-l-dihydroxyphenylalanine PET. Positron-emitting radiopharmaceuticals for somatostatin receptor (SSTR) imaging—DOTA analogs, which include 68Ga-DOTATATE, 68Ga-DOTATOC, and 68Ga-DOTANOC—have a high affinity to SSTRs, especially to SSTR2. Recently, several studies have demonstrated that when 68Ga-labeled somatostatin analog PET is combined with CT, sensitivity for detecting neuroendocrine tumors is higher than with SSTR scintigraphy. A metaanalysis study suggested that 68Ga-DOTATATE is most accurate for detecting neuroendocrine tumors (2).
MATERIALS AND METHODS
We performed 68Ga DOTATATE PET/CT on 3 patients with insulinoma and evaluated its usefulness as a first-choice imaging method. Written informed consent was obtained from all patients. All 3 patients had fasting hypoglycemia and received a biochemical diagnosis of insulinoma when they experienced inappropriately high serum insulin concentrations during a 72-h fast. Imaging techniques were then used to localize the tumor.
The first patient was a 49-y-old woman who had complaints of repeated episodes of hypoglycemia and weight gain. Capillary glucose measured by a health professional was 47 mg/dL, and the patient improved after receiving intravenous glucose. After fasting for 10 h, she became diaphoretic and confused. Serum values at that time were as follows: glucose, 44 mg/dL; insulin, 22.3 microunits/mL; and C-peptide, 3.06 ng/mL. Spiral CT of the abdomen revealed a mass at the body of the pancreas, and 68Ga-DOTATATE PET/CT was performed.
The second patient was a 59-y-old woman who had complaints of headache and sweating. After fasting for 6 h, she became hypoglycemic. Serum values at that time were as follows: glucose, 53 mg/dL; insulin, 37 microunits/mL; and C-peptide, 4.14 ng/mL. Spiral CT of the abdomen showed no visible mass, and 68Ga-DOTATATE PET/CT was performed.
The third patient was a 55-y-old woman who had complaints of headache. After fasting for 12 h, she became hypoglycemic. Serum values at that time were as follows: glucose, 36 mg/dL; insulin,11.43 microunits/mL; and C-peptide, 2.32 ng/mL. Spiral CT of the abdomen showed no visible mass, and 68Ga-DOTATATE PET/CT was performed.
RESULTS
In all 3 patients, insulinoma was clearly shown on 68Ga-DOTATATE PET/CT: at the body of the pancreas in patient 1 (Fig. 1), at the body of the pancreas in patient 2 (Fig. 2), and at the tail of the pancreas in patient 3 (Fig. 3).
68Ga DOTATATE PET/CT showing lesion at body of pancreas (patient 1). A color version of this figure is available as a supplemental file at http://tech.snmjournals.org.
68Ga DOTATATE PET/CT showing lesion at body of pancreas (patient 2). A color version of this figure is available as a supplemental file at http://tech.snmjournals.org.
68Ga DOTATATE PET/CT showing lesion at tail of pancreas (patient 3). A color version of this figure is available as a supplemental file at http://tech.snmjournals.org.
In the first patient, the insulinoma was confirmed by intraoperative ultrasonography, enucleated, and confirmed pathologically. In the second, oral diazoxide was started after the 68Ga-DOTATATE PET/CT examination, and surgery was planned. In the third, the insulinoma was confirmed by intraoperative ultrasonography, and distal pancreatectomy was performed; pathologic examination confirmed insulinoma.
DISCUSSION
Accurate preoperative localization of an insulinoma is desirable because some tumors may not be palpable at the time of surgery (1). The noninvasive procedures available include spiral CT, MRI, transabdominal ultrasonography, 111In-pentetreotide imaging, and 18F-l-dihydroxyphenylalanine PET. Our patients had biochemically proven insulinomas, but noninvasive procedures were able to show insulinoma in only 1 of the 3 patients.
In patients with an established insulinoma and negative results on noninvasive radiologic localization studies, endoscopic ultrasonography or selective arterial calcium stimulation testing with hepatic venous sampling can be performed to localize the tumor. These procedures are invasive, and skilled personnel are necessary. The choice of procedure depends on which test is available and local level of radiologic skill. In our center, we cannot use these invasive procedures. Because most neuroendocrine tumors express SST receptors, they can be effectively targeted and visualized with radiolabeled SST analogs in vivo. Pentetreotide scintigraphy can be used to localize insulinomas but will miss 40% of them.
Most studies have demonstrated the potential of PET technology using 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE. In particular, PET clearly offers higher resolution and better pharmacokinetics than SST receptor scintigraphy, with promising results for detecting SST receptor–expressing tumors and providing prognostic information (2). Recently, PET with the 68Ga-DOTA–conjugated peptides 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE has brought about dramatic improvements in spatial resolution. Use of these agents in specialized centers is increasing. 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE can bind to SST receptor 2, but they have different affinity profiles for other SST receptor subtypes. In particular, 68Ga-DOTANOC also shows a good affinity for SST receptors 3 and 5, 68Ga-DOTATOC also binds to SST receptor 5, and 68Ga-DOTATATE has a predominant affinity for SST receptor 2. A study demonstrated that SSTR2 and SSTR5 are the major SSTRs expressed in insulinomas (3). These findings suggest that 68Ga-DOTATATE has high affinity for SSTR2 and SSTR5 and thus, when positive in a biochemically proven patient, is specific for insulinomas as observed in our patient. It has been previously reported that 68Ga-DOTATATE PET/CT can detect neuroendocrine tumors as small as 6 mm. 68Ga-DOTATATE PET/CT can be helpful to localized small insulinomas.
In the literature, there are two case reports on the use of 68Ga-DOTATATE PET/CT as a successful imaging method to detect insulinomas (4,5). In our study, all patients’ insulinomas were shown clearly with 68Ga-DOTATATE PET/CT. In a study by Prasad et al., it was observed that tumor localization was compatible with DOTATATE in patients with insulinoma (6). A study by Nockel et al. showed localization to be accurate in pathologically proven patients with 68Ga-DOTATATE PET/CT insulinoma (7).
CONCLUSION
68Ga-DOTATATE PET/CT can be alternative imaging method for patients with negative results on noninvasive radiologic localization studies, as well as an alternative to invasive methods such as selective arterial calcium stimulation testing. To our knowledge, ours was one of the first attempts to detect insulinoma by the use of 68Ga-DOTATATE PET/CT. Larger studies are needed to confirm our results.
DISCLOSURE
No potential conflict of interest relevant to this article was reported.
Footnotes
Published online Aug. 10, 2017.
REFERENCES
- Received for publication December 8, 2016.
- Accepted for publication May 31, 2017.
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