Universität zu Köln

Vazquez, Sergio Munoz, Endepols, Heike, Fischer, Thomas, Tawadros, Samir-Ghali, Hohberg, Melanie, Zimmermanns, Beate, Dietlein, Felix, Neumaier, Bernd, Drzezga, Alexander ORCID: 0000-0001-6018-716X, Dietlein, Markus and Schomaecker, Klaus (2022). Translational Development of a Zr-89-Labeled Inhibitor of Prostate-specific Membrane Antigen for PET Imaging in Prostate Cancer. Mol. Imaging. Biol., 24 (1). S. 115 - 126. NEW YORK: SPRINGER. ISSN 1860-2002

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Abstract

Purpose We present here a Zr-89-labeled inhibitor of prostate-specific membrane antigen (PSMA) as a complement to the already established F-18- or Ga-68-ligands. Procedures The precursor PSMA-DFO (ABX) was used for Zr-89-labeling. This is not an antibody, but a peptide analogue of the precursor for the production of [Lu-177]Lu-PSMA-617. The ligand [Zr-89]Zr-PSMA-DFO was compared with [Ga-68]Ga-PSMA-11 and [F-18]F-JK-PSMA-7 in vitro by determination of the K-d value, cellular uptake, internalization in LNCaP cells, biodistribution studies with LNCaP prostate tumor xenografts in mice, and in vivo by small-animal PET imaging in LNCaP tumor mouse models. A first-in-human PET was performed with [Zr-89]Zr-PSMA-DFO on a patient presenting with a biochemical recurrence after brachytherapy and an ambiguous intraprostatic finding with [F-18]F-JK-PSMA-7 but histologically benign cells in a prostate biopsy 7 months previously. Results [Zr-89]Zr-PSMA-DFO was prepared with a radiochemical purity >= 99.9% and a very high in vitro stability for up to 7 days at 37 degrees C. All radiotracers showed similar specific cellular binding and internalization, in vitro and comparable tumor uptake in biodistribution experiments during the first 5 h. The [Zr-89]Zr-PSMA-DFO achieved significantly higher tumor/background ratios in LNCaP tumor xenografts (tumor/blood: 309 +/- 89, tumor/muscle: 450 +/- 38) after 24 h than [Ga-68]Ga-PSMA-11 (tumor/blood: 112 +/- 57, tumor/muscle: 58 +/- 36) or [F-18]F-JK-PSMA-7 (tumor/blood: 175 +/- 30, tumor/muscle: 114 +/- 14) after 4 h (p < 0.01). Small-animal PET imaging demonstrated in vivo that tumor visualization with [Zr-89]Zr-PSMA-DFO is comparable to [Ga-68]Ga-PSMA-11 or [F-18]F-JK-PSMA-7 at early time points (1 h p.i.) and that PET scans up to 48 h p.i. clearly visualized the tumor at late time points. A late [Zr-89]Zr-PSMA-DFO PET scan on a patient with biochemical recurrence (BCR) had demonstrated intensive tracer accumulation in the right (SUVmax 13.25, 48 h p.i.) and in the left prostate lobe (SUV max 9.47), a repeat biopsy revealed cancer cells on both sides. Conclusion [Zr-89]Zr-PSMA-DFO is a promising PSMA PET tracer for detection of tumor areas with lower PSMA expression and thus warrants further clinical evaluation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vazquez, Sergio Munoz UNSPECIFIED UNSPECIFIED UNSPECIFIED Endepols, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Tawadros, Samir-Ghali UNSPECIFIED UNSPECIFIED UNSPECIFIED Hohberg, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmermanns, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Dietlein, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED orcid.org/0000-0001-6018-716X UNSPECIFIED Dietlein, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Schomaecker, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-587702
DOI:	10.1007/s11307-021-01632-x
Journal or Publication Title:	Mol. Imaging. Biol.
Volume:	24
Number:	1
Page Range:	S. 115 - 126
Date:	2022
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1860-2002
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BIOCHEMICAL RECURRENCE; EMISSION-TOMOGRAPHY; THERAPY; ZR-89; EXPRESSION; CELLS Multiple languages Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58770