Universität zu Köln

Endepols, Heike ORCID: 0000-0002-6166-4818, Morgenroth, Agnieszka, Zlatopolskiy, Boris D., Krapf, Philipp ORCID: 0000-0003-1671-2443, Zischler, Johannes, Richarz, Raphael, Vasquez, Sergio Munoz, Neumaier, Bernd ORCID: 0000-0001-5425-3116 and Mottaghy, Felix M. (2019). Peripheral ganglia in healthy rats as target structures for the evaluation of PSMA imaging agents. BMC Cancer, 19. LONDON: BMC. ISSN 1471-2407

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Abstract

BackgroundThe recent implementation of PET with prostate specific membrane antigen (PSMA)-specific radiotracers into the clinical practice has resulted in the significant improvement of accuracy in the detection of prostate carcinoma (PCa). PSMA-expression in ganglia has been regarded as an important pitfall in prostate carcinoma-PET diagnostics but has not found any practical use for diagnosis or therapy.MethodsWe explored this phenomenon and demonstrated the applicability of peripheral ganglia in healthy rats as surrogates for small PSMA positive lesions for the preclinical evaluation of diagnostic PCa PET probes. Healthy rats were measured with PET/CT using the tracers [F-18]DCFPyL, [(AlF)-F-18]PSMA-11 and [Ga-68]PSMA-11. Sections of ganglia were stained with an anti-PSMA antibody. [F-18]DCFPyL uptake in ganglia was compared to that in LNCaP tumor xenografts in mice.ResultsWhereas [F-18]DCFPyL and [Ga-68]PSMA-11 were stable in vivo and accumulated in peripheral ganglia, [(AlF)-F-18]PSMA-11 suffered from fast in vivo deflourination resulting in high bone uptake. Ganglionic PSMA expression was confirmed by immunohistochemistry. [F-18]DCFPyL uptake and signal-to-noise ratio in the superior cervical ganglion was not significantly different from LNCaP xenografts.ConclusionsOur results demonstrated the non-inferiority of the novel model compared to conventionally used tumor xenografts in immune compromised rodents with regard to reproducibility and stability of the PSMA signal. Furthermore, the model involves less expense and efforts while it is permanently available and avoids tumor-growth associated animal morbidity and distress. To the best of our knowledge, this is the first tumor-free model suitable for the in vivo evaluation of tumor imaging agents.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Endepols, Heike UNSPECIFIED orcid.org/0000-0002-6166-4818 UNSPECIFIED Morgenroth, Agnieszka UNSPECIFIED UNSPECIFIED UNSPECIFIED Zlatopolskiy, Boris D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Krapf, Philipp UNSPECIFIED orcid.org/0000-0003-1671-2443 UNSPECIFIED Zischler, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Richarz, Raphael UNSPECIFIED UNSPECIFIED UNSPECIFIED Vasquez, Sergio Munoz UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED orcid.org/0000-0001-5425-3116 UNSPECIFIED Mottaghy, Felix M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-137436
DOI:	10.1186/s12885-019-5841-8
Journal or Publication Title:	BMC Cancer
Volume:	19
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1471-2407
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MEMBRANE ANTIGEN; PROSTATE; EXPRESSION; PET; THERAPY; MOUSE; CELLS Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13743