To chelate thallium(I) - synthesis and evaluation of Kryptofix-based chelators for 201 Tl.

Autor:	Frei A; Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, W12 0BZ, UK. a.frei@imperial.ac.uk.; School of Biomedical Engineering and Imaging Sciences, King's College London, 4th Floor Lambeth Wing, St Thomas' Hospital, London, SE1 7EH, UK., Rigby A; School of Biomedical Engineering and Imaging Sciences, King's College London, 4th Floor Lambeth Wing, St Thomas' Hospital, London, SE1 7EH, UK., Yue TTC; Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, W12 0BZ, UK. a.frei@imperial.ac.uk.; School of Biomedical Engineering and Imaging Sciences, King's College London, 4th Floor Lambeth Wing, St Thomas' Hospital, London, SE1 7EH, UK., Firth G; School of Biomedical Engineering and Imaging Sciences, King's College London, 4th Floor Lambeth Wing, St Thomas' Hospital, London, SE1 7EH, UK., Ma MT; School of Biomedical Engineering and Imaging Sciences, King's College London, 4th Floor Lambeth Wing, St Thomas' Hospital, London, SE1 7EH, UK., Long NJ; Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London, W12 0BZ, UK. a.frei@imperial.ac.uk.
Jazyk:	angličtina
Zdroj:	Dalton transactions (Cambridge, England : 2003) [Dalton Trans] 2022 Jun 13; Vol. 51 (23), pp. 9039-9048. Date of Electronic Publication: 2022 Jun 13.
DOI:	10.1039/d2dt01074g
Abstrakt:	While best known for its toxic properties, thallium has also been explored for applications in nuclear diagnostics and medicine. Indeed, [ 201 Tl]TlCl has been used extensively for nuclear imaging in the past before it was superceded by other radionuclides such as 99m Tc. One reason for this loss of interest is the severe lack of suitable organic chelators able to effectively coordinate ionic forms of Tl and deliver it to specific diseased tissue by means of attached biological vectors. Herein, we describe the synthesis and characterisation of a series of Kryptofix 222-based chelators that can be radiolabelled with 201 Tl(I) in high radiochemical yields at ambient temperature. We demonstrate that from these simple chelators, targeted derivatives are readily accessible and describe the synthesis and preliminary biological evaluation of a PSMA-targeted 201 Tl-labelled Kryptofix 222-peptide conjugate. While the Kryptofix system is demonstrably capable of binding the thallium cation, no PSMA-mediated cell-uptake could be detected with the PSMA conjugate, suggesting that this targeting moiety may not be ideal for use in conjunction with 201 Tl.
Databáze:	MEDLINE
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