Synthesis of [64Cu]DOTA-ADIBON3-Ala-PEG28-A20FMDV2 via copper-free click chemistry for PET imaging of integrin αvβ6

Drishty Satpati, Nadine Bauer, Sven H. Hausner, Julie Sutcliffe

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Catalyst-free click reactions are effective chemical tools for synthesis of radiometal-based radiopharmaceuticals offering advantages towards preparation of non-toxic agents with high specific activity. In the present study the radiotracer [64Cu]DOTA-ADIBON3-Ala-PEG28-A20FMDV2, [64Cu]3, was synthesized for positron emission tomography imaging of integrin αvβ6 expressing tumors via a strain-promoted click reaction using both a “pre-click” and “post-click” approaches. The radiotracer, prepared in >99% radiochemical yield, was evaluated in vitro (64.6±2.8% binding to αvβ6-positive cells vs. <5% to αvβ6-negative cells) and in vivo (αvβ6-positive tumor uptake: 1.52±0.16% ID/g, 24h p.i.). While the high initial renal uptake (76.2±10.7% ID/g at 1h p.i.) was comparable to a previously reported radiotracer, [64Cu]DOTA-PEG28-A20FMDV2, [64Cu]3 showed notably improved renal clearance (11.3±2.5% ID/g at 24h p.i.). Thus, the introduction of a chelator-strained alkyne system resulted in improved pharmacokinetics for the present radiotracer, highlighting the attractive prospects of strain-promoted click-based preparations in the construction of radiometalated bioconjugates for targeted molecular imaging and therapy.

Original languageEnglish (US)
Pages (from-to)765-771
Number of pages7
JournalJournal of Radioanalytical and Nuclear Chemistry
Volume302
Issue number2
DOIs
StatePublished - Oct 15 2014

Fingerprint

Click Chemistry
Integrins
Tumors
Copper
Molecular Targeted Therapy
Kidney
Molecular imaging
Imaging techniques
Positron emission tomography
Molecular Imaging
Pharmacokinetics
Alkynes
Radiopharmaceuticals
Chelating Agents
Positron-Emission Tomography
Neoplasms
Cells
Catalysts
In Vitro Techniques

Keywords

  • Cu
  • A20FMDV2
  • Strain-promoted click
  • αβ Integrin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Nuclear Energy and Engineering
  • Health, Toxicology and Mutagenesis
  • Pollution
  • Public Health, Environmental and Occupational Health
  • Spectroscopy
  • Radiology Nuclear Medicine and imaging

Cite this

Synthesis of [64Cu]DOTA-ADIBON3-Ala-PEG28-A20FMDV2 via copper-free click chemistry for PET imaging of integrin αvβ6 . / Satpati, Drishty; Bauer, Nadine; Hausner, Sven H.; Sutcliffe, Julie.

In: Journal of Radioanalytical and Nuclear Chemistry, Vol. 302, No. 2, 15.10.2014, p. 765-771.

Research output: Contribution to journalArticle

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abstract = "Catalyst-free click reactions are effective chemical tools for synthesis of radiometal-based radiopharmaceuticals offering advantages towards preparation of non-toxic agents with high specific activity. In the present study the radiotracer [64Cu]DOTA-ADIBON3-Ala-PEG28-A20FMDV2, [64Cu]3, was synthesized for positron emission tomography imaging of integrin αvβ6 expressing tumors via a strain-promoted click reaction using both a “pre-click” and “post-click” approaches. The radiotracer, prepared in >99{\%} radiochemical yield, was evaluated in vitro (64.6±2.8{\%} binding to αvβ6-positive cells vs. <5{\%} to αvβ6-negative cells) and in vivo (αvβ6-positive tumor uptake: 1.52±0.16{\%} ID/g, 24h p.i.). While the high initial renal uptake (76.2±10.7{\%} ID/g at 1h p.i.) was comparable to a previously reported radiotracer, [64Cu]DOTA-PEG28-A20FMDV2, [64Cu]3 showed notably improved renal clearance (11.3±2.5{\%} ID/g at 24h p.i.). Thus, the introduction of a chelator-strained alkyne system resulted in improved pharmacokinetics for the present radiotracer, highlighting the attractive prospects of strain-promoted click-based preparations in the construction of radiometalated bioconjugates for targeted molecular imaging and therapy.",
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