A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Safety Study of Single-Dose Intravenously Administered DOTA-Siglec-9 Peptide in Sprague Dawley Rats
Tekijät: Chrusciel P, Yatkin E, Li XG, Jaakkola UM, Knuuti J, Jalkanen S, Roivainen A
Kustantaja: SAGE PUBLICATIONS INC
Julkaisuvuosi: 2019
Journal: International Journal of Toxicology
Tietokannassa oleva lehden nimi: INTERNATIONAL JOURNAL OF TOXICOLOGY
Lehden akronyymi: INT J TOXICOL
Vuosikerta: 38
Numero: 1
Aloitussivu: 4
Lopetussivu: 11
Sivujen määrä: 8
ISSN: 1091-5818
DOI: https://doi.org/10.1177/1091581818821606
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/39291599
The peptide-based radioactive compound [Ga-68]Ga-DOTA-Siglec-9 is a novel agent for imaging of inflammation with positron emission tomography. The drug target of [Ga-68]Ga-DOTA-Siglec-9 is vascular adhesion protein 1. Previous studies have obtained promising results with [Ga-68]Ga-DOTA-Siglec-9 in experimental animals. However, before taking this novel imaging agent into clinical trials, safety and toxicological studies need to be performed with the nonradioactive precursor compound DOTA-Siglec-9. This extended single-dose toxicity study was designed to provide information on the major toxic effects of DOTA-Siglec-9 and to indicate possible target organs after a single intravenous (iv) injection in rats. The study was performed using 60 adult Hsd: Sprague Dawley rats and included a control group and a treatment group to investigate the toxicity of DOTA-Siglec-9 solution at a final concentration of 0.2 mg/mL after a single iv injection of 582 mu g/kg. The maximum dose tested was 1,000-fold the clinical dose on a mg/kg basis as indicated in European Medicines Agency International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guideline M3(R2). The planned human clinical dose is approximately 0.582 mu g of DOTA-Siglec-9 per kg of body mass. This study demonstrates that iv administration of DOTA-Siglec-9 at a dose of 582 mu g/kg was well tolerated in rats and did not produce toxicologically significant adverse effects.
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