Feasibility of Insulinoma Radiotheranostics: [<sup>68</sup>Ga]Ga-DO3A-VS-Cys<sup>40</sup>-Exendin-4 and [<sup>177</sup>Lu]Lu-DO3A-VS-Cys<sup>40</sup>-Exendin-4 — ASN Events
  1. Schedule
  2. Conference Breakfast: Moderated Poster Walk - Neuroendocrine tumours
  3. Feasibility of Insulinoma Radiotheranostics: [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 and [177Lu]Lu-DO3A-VS-Cys40-Exendin-4

Feasibility of Insulinoma Radiotheranostics: [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 and [177Lu]Lu-DO3A-VS-Cys40-Exendin-4 (#126)

Irina Velikyan 1 2 , Ramkumar Selvaraju 3 , Ulrika Rosenström 3 , Jens Sörensen 1 , Gunnar Antoni 3 , Olle Korsgren 4 , Barbro Eriksson 5 , Olof Eriksson 3
  1. Section of Nuclear Medicine and PET, Department of Surgical Sciences , Uppsala University Hospital, Uppsala, Sweden
  2. PET-Centre, Uppsala University Hospital, Uppsala, Sweden
  3. Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
  4. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  5. Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden

Glucagon like peptide-1 receptor (GLP-1R) is expressed in insulinomas. Targeting GLP-1R with various 68Ga-labelled Exendin-4 analogues has been proven a valuable clinical means for the accurate lesion detection and receptor expression quantification with positron emission tomography (PET). The first line treatment is the surgical removal of the lesions, however the localization of the lesions is a complex process especially in the paediatric patients. Thus the GLP-1R targeted internal radiotherapy would be of outmost importance and would provide personalized treatment possibility.

            Preclinical studies using [68Ga]Ga/[177Lu]Lu-DO3A-VS-Cys40-Exendin-4 were performed in INS-1 tumor biopsy, INS-1 xenografted mice, Lewis rats, pigs, and non-human primates. Clinical study with [68Ga]Ga-DO3A-VS-Cys40-Exendin-4/PET was performed in a female patient. Dosimetry estimations were performed in rats, pigs, non-human primates, and a human for [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 and in rats for [177Lu]Lu-DO3A-VS-Cys40-Exendin-4.   

            The dissociation constant of 3.1 nM and receptor density of 175.8 pmol/mg were determined. High image contrast and accurate localization of lesions were observed. Fast blood clearance and washout from all organs except for kidneys were shown for both [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 and [177Lu]Lu-DO3A-VS-Cys40-Exendin-4. The kidney was the dose-limiting organ with absorbed dose of 0.38 (female)/0.30 (male) mGy/MBq and 5.88 (female)/6.04 (male) mGy/MBq, respectively for [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 and [177Lu]Lu-DO3A-VS-Cys40-Exendin-4. Estimation of the tumor absorbed dose for [177Lu]Lu-DO3A-VS-Cys40-Exendin-4 was made based on the clinical study using the 68Ga-counterpart, and resulted in 3.9 GBq per one radiotherapeutic cycle that might not be sufficient to control the tumor growth.

            Although both agents demonstrate highly specific binding to GLP-1R and similar organ distribution pattern, the high absorbed dose to kidneys put constrains on their application in the context of radiotheranostics. At least six annual examinations can be performed using [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 and allowing treatment response monitoring. However, radiotherapeutic application of [177Lu]-DO3A-VS-Cys40-Exendin-4 might be futile and require further development in order to minimize the kidney uptake.