Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan

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. Maxadi...

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Autores principales:	Lieke Joosten, Maarten Brom, Martin K. H. Schäfer, Otto C. Boerman, Eberhard Weihe, Martin Gotthardt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15cd8f038ddf48b98c71877b796995fd
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spelling	oai:doaj.org-article:15cd8f038ddf48b98c71877b796995fd2021-12-02T11:40:21ZPreclinical evaluation of PAC1 targeting with radiolabeled Maxadilan10.1038/s41598-017-01852-82045-2322https://doaj.org/article/15cd8f038ddf48b98c71877b796995fd2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01852-8https://doaj.org/toc/2045-2322Abstract 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 to the PAC1 receptor was maintained after DTPA conjugation. Furthermore, radiolabeled maxadilan-DTPA accumulated specifically in INS-1 tumors and, therefore, may qualify as a useful tracer to image insulinomas.Lieke JoostenMaarten BromMartin K. H. SchäferOtto C. BoermanEberhard WeiheMartin GotthardtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lieke Joosten Maarten Brom Martin K. H. Schäfer Otto C. Boerman Eberhard Weihe Martin Gotthardt Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan
description	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 to the PAC1 receptor was maintained after DTPA conjugation. Furthermore, radiolabeled maxadilan-DTPA accumulated specifically in INS-1 tumors and, therefore, may qualify as a useful tracer to image insulinomas.
format	article
author	Lieke Joosten Maarten Brom Martin K. H. Schäfer Otto C. Boerman Eberhard Weihe Martin Gotthardt
author_facet	Lieke Joosten Maarten Brom Martin K. H. Schäfer Otto C. Boerman Eberhard Weihe Martin Gotthardt
author_sort	Lieke Joosten
title	Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan
title_short	Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan
title_full	Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan
title_fullStr	Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan
title_full_unstemmed	Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan
title_sort	preclinical evaluation of pac1 targeting with radiolabeled maxadilan
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/15cd8f038ddf48b98c71877b796995fd
work_keys_str_mv	AT liekejoosten preclinicalevaluationofpac1targetingwithradiolabeledmaxadilan AT maartenbrom preclinicalevaluationofpac1targetingwithradiolabeledmaxadilan AT martinkhschafer preclinicalevaluationofpac1targetingwithradiolabeledmaxadilan AT ottocboerman preclinicalevaluationofpac1targetingwithradiolabeledmaxadilan AT eberhardweihe preclinicalevaluationofpac1targetingwithradiolabeledmaxadilan AT martingotthardt preclinicalevaluationofpac1targetingwithradiolabeledmaxadilan
_version_	1718395625148514304

Preclinical evaluation of PAC1 targeting with radiolabeled Maxadilan

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