Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan

Scientific Reports
Lieke JoostenMartin Gotthardt

Abstract

There is an ongoing search for new tracers to optimize imaging of beta cell-derived tumors (insulinomas). The PAC1 receptor, expressed by insulinomas, can be used for targeting of these tumors. Here, we investigated whether radiolabeled maxadilan could be used for insulinoma imaging. Maxadilan was C- or N-terminally conjugated with DTPA (termed maxadilan-DPTA or DTPA-maxadilan respectively). BALB/c nude mice bearing subcutaneous INS-1 tumors were injected with either In-111-labeled maxadilan-DTPA or In-111-DTPA-maxadilan. Biodistribution studies were carried out at 1, 2 and 4 hours after injection and SPECT/CT imaging 1 and 4 hours after injection of maxadilan-DTPA-111In. Radiolabeling of maxadilan-DTPA (680 MBq/nmol) was more efficient than of DTPA-maxadilan (55 MBq/nmol). Conjugation with DTPA slightly reduced receptor binding affinity in vitro: IC50 values were 3.2, 21.0 and 21.0 nM for maxadilan, natIn-DTPA-maxadilan and maxadilan-DTPA-natIn respectively. Upon i.v. injection maxadilan-DTPA-111In accumulated specifically in INS-1 tumors (7.30 ± 1.87%ID/g) and in the pancreas (3.82 ± 0.22%ID/g). INS-1 tumors were clearly visualized by small animal SPECT/CT. In conclusion, this study showed that the high affinity of maxadilan ...Continue Reading

References

Apr 1, 1996·Journal of Cellular Physiology·P VertongenP Robberecht
Dec 26, 1996·Annals of the New York Academy of Sciences·N InagakiS Seino
Nov 24, 1999·The Journal of Clinical Investigation·N ZengJ R Pisegna
Apr 23, 2003·European Journal of Nuclear Medicine and Molecular Imaging·Jean Claude Reubi, Beatrice Waser
Aug 8, 2007·Peptides·Ethan A LernerVemuri B Reddy
Aug 16, 2008·The New England Journal of Medicine·Damian WildJean Claude Reubi
Dec 17, 2008·Annals of the New York Academy of Sciences·Bo Ahrén
Oct 13, 2009·The Journal of Clinical Endocrinology and Metabolism·Emanuel ChristJean Claude Reubi
Jan 30, 2010·European Journal of Nuclear Medicine and Molecular Imaging·Maarten BromOtto C Boerman
Jul 3, 2010·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Damian WildHelmut R Mäcke
Nov 26, 2010·Endocrinology and Metabolism Clinics of North America·Emanuel ChristJean Claude Reubi
Jun 18, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Damian WildJean Claude Reubi
Dec 16, 2011·European Journal of Nuclear Medicine and Molecular Imaging·Dale O KiesewetterXiaoyuan Chen
Mar 22, 2012·Contrast Media & Molecular Imaging·Maarten BromOtto C Boerman
Dec 12, 2012·European Journal of Nuclear Medicine and Molecular Imaging·Anna Sowa-StaszczakAlicja Hubalewska-Dydejczyk
Jan 25, 2014·European Journal of Endocrinology·Pedro Iglesias, Juan J Díez
Feb 12, 2014·The Journal of Clinical Endocrinology and Metabolism·Olof ErikssonOlle Korsgren
Mar 14, 2014·The Lancet. Diabetes & Endocrinology·Emanuel ChristFlavio Forrer
May 28, 2014·International Journal of Surgery·Andrea CavallaroAlessandro Cappellani
Aug 15, 2014·European Journal of Endocrinology·Wouter A van der ZwanDik J Kwekkeboom
Sep 18, 2014·Neuroendocrinology·Lisa BodeiIrvin M Modlin
Feb 24, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jean Claude Reubi, Beatrice Waser
May 23, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Kwadwo AntwiDamian Wild
Dec 26, 2015·Current Opinion in Endocrinology, Diabetes, and Obesity·Terry W MoodyRobert T Jensen
Mar 1, 2016·European Journal of Nuclear Medicine and Molecular Imaging·Vikas PrasadOliver Blankenstein
Mar 15, 2016·Best Practice & Research. Clinical Endocrinology & Metabolism·Tobias BaumannDamian Wild
Apr 30, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Svetlana N RylovaHelmut R Maecke

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts
imaging techniques

Software Mentioned

OSEM
- Rec
SPECT
GraphPad Prism
GraphPad

Related Concepts

Related Feeds

Adenoma, Islet Cell

Islet Cell Adenoma arises in the islet cells, which are insulin producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Adenoma here.