Outcomes of 68Ga-NODAGA-Exendin-4 PET/CT Guided Surgical Management
                    of Insulinomas in MEN1: A Preliminary Study

Ketki Sunil Ambulkar; Ravikumar Shah; Anurag Lila; Anima Sharma; Rohit Barnabas; Manjiri Karlekar; Saba Samad Memon; Vijaya Sarathi; Sameer Rege; Priyanka Verma; Gaurav Malhotra; Vikram Lele; Tushar Bandgar

doi:10.1055/a-2620-2931

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2025; 57(06): 366-372
DOI: 10.1055/a-2620-2931

Original Article: Endocrine Care

Outcomes of 68Ga-NODAGA-Exendin-4 PET/CT Guided Surgical Management of Insulinomas in MEN1: A Preliminary Study

Ketki Sunil Ambulkar‡

¹Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)

,

Ravikumar Shah‡

²Harikrushna Hormone Clinic, Anand, India

,

Anurag Lila

¹Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)

,

Anima Sharma

¹Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)

,

Rohit Barnabas

¹Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)

,

Manjiri Karlekar

¹Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)

,

Saba Samad Memon

¹Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)

,

Vijaya Sarathi

³Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, India (Ringgold ID: RIN29549)

,

Sameer Rege

⁴Department of General Surgery, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)

,

Priyanka Verma

⁵Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India (Ringgold ID: RIN75893)

,

Gaurav Malhotra

⁵Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India (Ringgold ID: RIN75893)

,

Vikram Lele

⁶Department of Nuclear Medicine, Jaslok Hospital & Research Center, Mumbai, India (Ringgold ID: RIN29445)

,

Tushar Bandgar

¹Department of Endocrinology and Metabolism, Seth GS Medical College and KEM Hospital, Mumbai, India (Ringgold ID: RIN29549)

› Author Affiliations

Abstract

The data on the use of 68Ga-NODAGA-exendin-4 PET/CT in localizing multiple endocrine neoplasia type 1 (MEN1)-related insulinomas is evolving; however, surgical outcomes data are not available. We describe our cohort of patients with MEN1-related endogenous hyperinsulinemic hypoglycemia (EHH), where 68Ga-NODAGA-exendin-4 PET/CT was used to guide conservative surgery. A retrospective record review of MEN1-related EHH cases managed between 2000 and 2024 was performed for clinical features, imaging, and management. Outcomes were assessed for patients whose surgical extent was determined by 68Ga-NODAGA-exendin-4 PET/CT versus conventional imaging (CECT and 68Ga-DOTATATE PET/CT). Five patients with a median age of 17 (15.5–18.5 years) with EHH underwent laparoscopic, single lesion enucleation based on 68Ga-NODAGA-exendin-4 PET/CT. On preoperative imaging, CT identified culprit lesion in four, while 68Ga-DOTATATE PET/CT localized in one, and had one false positive uptake in non-functioning NET. The median duration of hospital stay was 6 (5.5–9) days. Over a median follow-up of 48 (3.5–84.5) months, none had EHH recurrence or exocrine/endocrine pancreatic insufficiency. On follow-up, one patient had an uneventful pregnancy and delivery. In the remaining 15, who underwent surgery based on conventional imaging, 12 (80%) required extensive surgery beyond enucleation, of which two needed intraoperative ultrasound localization. This group had a postoperative hospital stay of 11 (8–23) days, one recurrence after 84 months, and pancreatic insufficiency in 5 (33%). Our center observation suggests that GLP1R-based PET/CT-guided conservative insulinoma surgery in MEN1 patients is effective and safe and needs further validation.

Keywords

MEN1 - exendin - GLP1 - surgical outcomes - insulinoma - endogenous hyperinsulinemic hypoglycemia

Full Text

References

References
1 Hofland J, Refardt JC, Feelders RA. et al. Approach to the patient: insulinoma. J Clin Endocrinol Metab 2024; 109: 1109-1118
2 Shah R, Garg R, Majmundar M. et al. Exendin-4-based imaging in insulinoma localization: systematic review and meta-analysis. Clin Endocrinol (Oxf) 2021; 95: 354-364
3 Guettier J-M, Kam A, Chang R. et al. Localization of insulinomas to regions of the pancreas by intraarterial calcium stimulation: the NIH experience. J Clin Endocrinol Metab 2009; 94: 1074-1080
4 van Beek DJ, Nell S, Verkooijen HM. et al. Surgery for multiple endocrine neoplasia type 1-related insulinoma: long-term outcomes in a large international cohort. Br J Surg 2020; 107: 1489-1499
5 Triponez F, Sadowski SM, Pattou F. et al. Long-term follow-up of MEN1 patients who do not have initial surgery for small≤2 cm nonfunctioning pancreatic neuroendocrine tumors, an AFCE and GTE study: Association Francophone de Chirurgie Endocrinienne & Groupe d’Etude des Tumeurs Endocrines. Ann Surg 2018; 268: 158-16
6 Chatzipanagiotou O, Schizas D, Vailas M. et al. All you need to know about gastrinoma today | gastrinoma and Zollinger-Ellison syndrome: a thorough update. J Neuroendocrinol 2023; 35: e13267
7 Thakker RV, Newey PJ, Walls GV. et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 2012; 97: 2990-3011
8 Christ E, Wild D, Ederer S. et al. Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study. Lancet Diabetes Endocrinol 2013; 1: 115-122
9 Luo Y, Pan Q, Yao S. et al. Glucagon-like peptide-1 receptor PET/CT with 68Ga-NOTA-exendin-4 for detecting localized insulinoma: a prospective cohort study. J Nucl Med 2016; 57: 715-720
10 Antwi K, Nicolas G, Fani M. et al. 68Ga-Exendin-4 PET/CT detects insulinomas in patients with endogenous hyperinsulinemic hypoglycemia in MEN-1. J Clin Endocrinol Metab 2019; 104: 5843-5852
11 Sakurai A, Yamazaki M, Suzuki S. et al. Clinical features of insulinoma in patients with multiple endocrine neoplasia type 1: analysis of the database of the MEN consortium of Japan. Endocr J 2012; 59: 859-866
12 Vezzosi D, Cardot-Bauters C, Bouscaren N. et al. Long-term results of the surgical management of insulinoma patients with MEN1: a Groupe d’étude des Tumeurs Endocrines (GTE) retrospective study. Eur J Endocrinol 2015; 172: 309-319
13 Zhao Y, Yu J, Liu Y. et al. Analysis of 55 patients with multiple endocrine neoplasia type 1-associated insulinoma from a single center in China. Orphanet J Rare Dis 2022; 17: 219
14 Vesterinen T, Peltola E, Leijon H. et al. Immunohistochemical glucagon-like peptide-1 receptor expression in human insulinomas. Int J Mol Sci 2023; 24: 15164
15 Erichsen TD, Detlefsen S, Andersen KØ. et al. Occult insulinoma, glucagonoma and pancreatic endocrine pseudotumour in a patient with multiple endocrine neoplasia type 1. Pancreatology 2020; 20: 293-296
16 Liang M, Jiang J, Dai H. et al. Robotic enucleation for pediatric insulinoma with MEN1 syndrome: a case report and literature review. BMC Surg 2018; 18: 44
17 Sowa-Staszczak A, Pach D, Mikołajczak R. et al. Glucagon-like peptide-1 receptor imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 for the detection of insulinoma. Eur J Nucl Med Mol Imaging 2013; 40: 524-531
18 Xu J, Xu X, Zhang M. et al. Heterogeneity of multiple pancreatic neuroendocrine tumors identified by 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT in a patient with endogenous hyperinsulinemic hypoglycemia and multiple endocrine neoplasia 1. Neuroendocrinology 2024; 114: 866-871
19 Kent LA, Gill GV, Williams G. Mortality and outcome of patients with brittle diabetes and recurrent ketoacidosis. Lancet 1994; 344: 778-781
20 Roy A, Sahoo J, Kamalanathan S. et al. Islet cell dysfunction in patients with chronic pancreatitis. World J Diabetes 2020; 11: 280-292
21 Ichida H, Imamura H, Takahashi A. et al. Evaluation of pancreatic morphometric parameters, exocrine function, and nutritional status and their causal relationships in long-term survivors following pancreatectomy. Surgery 2024; 176: 1189-1197
22 Sada A, Habermann EB, Szabo Yamashita T. et al. Comparison between sporadic and multiple endocrine neoplasia type 1-associated insulinoma. J Am Coll Surg 2022; 235: 756-763

Supplementary Material

Supplementary Material