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Synthesis and preclinical evaluation of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand

  • Stefano Boschi
  • Jason T. Lee
  • Seval Beykan
  • Roger Slavik
  • Liu Wei
  • Claudio Spick
  • Uta Eberlein
  • Andreas K. Buck
  • Filippo Lodi
  • Gianfranco Cicoria
  • Johannes Czernin
  • Michael Lassmann
  • Stefano Fanti
  • Ken Herrmann
Original Article

Abstract

Purpose

The aim of this study was to synthesize and preclinically evaluate an 18F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined.

Methods

Several conditions for the labeling of 18F-PSMA-11 via 18F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed.

Results

Quantitative labeling yields could be achieved with >97 % radiochemical purity. The 18F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p < 4.2e-5). Results were confirmed by ex vivo gamma counter analysis of tissues after the last imaging time point. The highest absorbed dose was reported for the kidneys. The maximum effective dose for an administered activity of 200 MBq was 1.72 mSv.

Conclusion

18F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios. The kidneys were the dose-limiting organs. Even by applying the most stringent dosimetric calculations, injected activities of up to 0.56 GBq are feasible.

Keywords

PET PSMA 18Dosimetry Preclinical Prostate cancer 

Notes

Acknowledgment

We thank Larry Pang and Andreea Stuparu (members of the Ahmanson Translational Imaging Division) for their support and assistance.

Compliance with ethical standards

Funding

This study was partly supported by an unrestricted grant from the Movember Foundation—MOVEMBER GAP2 FUNDING AWARD.

Conflict of interest

Johannes Czernin is founder of Sofie Biosciences, which manufactures the Genisys4 scanner used in this manuscript. No other potential conflicts of interest are reported.

Ethical approval

Animal studies were approved by the UCLA Animal Research Committee and were carried out according to the guidelines of the Division of Laboratory Animal Medicine at UCLA. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants.

Author’s contributions

Initials: Stefano Boschi (SB), Jason T. Lee (JTL), Seval Beykan (SeB), Roger Slavik (RS), Liu Wei (LW), Uta Eberlein (UE), Andreas K. Buck (AKB), Filippo Lodi (FL), Gianfranco Coria (GC), Johannes Czernin (JC), Michael Lassmann (ML), Ken Herrmann (KH), Stefano Fanti (SF)

Conception and design: SB, AKB, JC, ML, KH, SF

Development of methodology: SB, JTL, RS, GC, ML, KH, SF

Acquisition of data: SB, JTL, RS, LW, FL, GC

Analysis and interpretation of data: JTL, SeB, RS, ML, KH, SF

Writing, review, and/or revision of the manuscript: all authors

Administrative, technical, or material support: SB, AKB, JC, ML, KH, SF

Supervision: SB, JC, ML, KH, SF

Supplementary material

259_2016_3437_MOESM1_ESM.doc (32 kb)
ESM 1 (DOC 32 kb)
259_2016_3437_MOESM2_ESM.doc (34 kb)
ESM 2 (DOC 33 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Stefano Boschi
    • 1
  • Jason T. Lee
    • 2
  • Seval Beykan
    • 3
  • Roger Slavik
    • 4
  • Liu Wei
    • 4
  • Claudio Spick
    • 4
  • Uta Eberlein
    • 3
  • Andreas K. Buck
    • 3
  • Filippo Lodi
    • 1
  • Gianfranco Cicoria
    • 5
  • Johannes Czernin
    • 4
  • Michael Lassmann
    • 3
  • Stefano Fanti
    • 1
  • Ken Herrmann
    • 3
    • 4
  1. 1.Department of Nuclear MedicineS.Orsola-Malpighi University HospitalBolognaItaly
  2. 2.Crump Institute for Molecular ImagingDavid Geffen School of Medicine at UCLALos AngelesUSA
  3. 3.Department of Nuclear MedicineUniversity Hospital WürzburgWürzburgGermany
  4. 4.Ahmanson Translational Imaging DivisionDavid Geffen School of Medicine at UCLALos AngelesUSA
  5. 5.Department of Medical PhysicsS. Orsola-Malpighi University HospitalBolognaItaly

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