Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer.

Matthias Eder,Ulrike Bauder-Wüst,Uwe Haberkorn,Martin Schäfer,Oliver Neels,Yvonne Remde,Ute Hennrich,Ali Afshar-Oromieh,Klaus Kopka,Miriam Müller,Michael Eisenhut

doi:10.3390/ph7070779

Abstract

The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA) has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective 68Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx) pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [68Ga]Ga-PSMA-HBED-CC.

Highlights

Detection of metastases or recurrent prostate cancer (PC) lesions is of utmost clinical relevance in terms of clinical staging, prognosis and therapy management [1,2]
The aim of this study is to summarize hitherto existing radiochemical experiences with HBED-CC
Specific cellular uptake was determined by competitive blocking with the prostate-specific membrane antigen (PSMA) inhibitor 2-(phosphonomethyl)pentanedioic acid

Summary

Introduction

Detection of metastases or recurrent prostate cancer (PC) lesions is of utmost clinical relevance in terms of clinical staging, prognosis and therapy management [1,2]. The high clinical impact of targeting the prostate-specific membrane antigen (PSMA) was recently demonstrated in a series of first-in-man examinations with either 68Ga- [3,4,5] or 123I-labelled [6] PSMA inhibitors. Since urea-based inhibitors of PSMA clear rapidly from the circulation and since only low levels of physiological PSMA expression were detected in a few organs like the brain, kidney, salivary gland and small intestine [7,9,10,11] PSMA represents an ideal biological target for high quality PET imaging of prostate cancer [12,13,14,15,16,17]. Initial clinical experiences with the 68Ga-labelled PET tracer Glu-NH-CO-NH-Lys-(Ahx)-[[68Ga]

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Conclusion