title: SPECT of Transplanted Islets of Langerhans by Dopamine 2 Receptor Targeting in a Rat Model.
abstract: Pancreatic islet transplantation can be a more permanent treatment for type 1 diabetes compared to daily insulin administration. Quantitative and longitudinal noninvasive imaging of viable transplanted islets might help to further improve this novel therapy. Since islets express dopamine 2 (D2) receptors, they could be visualized by targeting this receptor. Therefore, the D2 receptor antagonist based tracer [(125/123)I][IBZM] was selected to visualize transplanted islets in a rat model. BZM was radioiodinated, and the labeling was optimized for position 3 of the aromatic ring. [(125)I]-3-IBZM was characterized in vitro using INS-1 cells and isolated islets. Subsequently, 1,000 islets were transplanted in the calf muscle of WAG/Rij rats and SPECT/CT images were acquired 6 weeks after transplantation. Finally, the graft containing muscle was dissected and analyzed immunohistochemically. Oxidative radioiodination resulted in 3 IBZM isomers with different receptor affinities. The use of 0.6 mg/mL chloramine-T hydrate resulted in high yield formation of predominantly [(125)I]-3-IBZM, the isomer harboring the highest receptor affinity. The tracer showed D2 receptor mediated binding to isolated islets in vitro. The transplant could be visualized by SPECT 6 weeks after transplantation. The transplants could be localized in the calf muscle and showed insulin and glucagon expression, indicating targeting of viable and functional islets in the transplant. Radioiodination was optimized to produce high yields of [(125)I]-3-IBZM, the isomer showing optimal D2R binding. Furthermore, [(123)I]IBZM specifically targets the D2 receptors on transplanted islets. In conclusion, this tracer shows potential for noninvasive in vivo detection of islets grafted in the muscle by D2 receptor targeting.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Stefanie M A
authors.initials: SM
authors.lastname: Willekens
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: van der Kroon
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Lieke
authors.initials: L
authors.lastname: Joosten
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Cathelijne
authors.initials: C
authors.lastname: Frielink
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.affiliation: FutureChemistry Holding BV , Toernooiveld 100, 6525 EC Nijmegen, The Netherlands.
authors.forename: Sebastiaan A M W
authors.initials: SA
authors.lastname: van den Broek
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Brom
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Gotthardt
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry; D007457:Iodine Radioisotopes / Q000737:chemistry*; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D011759:Pyrrolidines / Q000737:chemistry; D051381:Rats; D011954:Receptors, Dopamine / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D011954:Receptors, Dopamine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide
keywords: IBZM; SPECT; iodination; islets of Langerhans; transplantation