Optimizing tumor targeting of the lipophilic EGFR-binding radiotracer SKI 243 using a liposomal nanoparticle delivery system Journal Article


Authors: Medina, O. P.; Pillarsetty, N.; Glekas, A.; Punzalan, B.; Longo, V.; Gonen, M.; Zanzonico, P.; Smith-Jones, P.; Larson, S. M.
Article Title: Optimizing tumor targeting of the lipophilic EGFR-binding radiotracer SKI 243 using a liposomal nanoparticle delivery system
Abstract: Positron emission tomography (PET) of epidermal growth factor receptor (EGFR) kinase-specific radiolabeled tracers could provide a means for non-invasively characterizing EGFR expression and signaling activity in patients' tumors before, during, and after therapy with EGFR inhibitors. Towards this goal, our group has developed PET tracers which irreversibly bind to EGFR. However, tumor uptake is relatively low because of both the lipophilicity of such tracers (e.g. the morpholino-[124I]-IPQA [SKI 212243]), with octanol-to-water partition coefficients of up to 4, and a short dwell time in the blood and significant hepatobiliary clearance and intestinal reuptake. Liposomal nanoparticle delivery systems may favorably alter the pharmacokinetic profile and improve tumor targeting of highly lipophilic but otherwise promising cancer imaging tracers, such as the EGFR inhibitor SKI 243. SKI 243 is therefore an interesting model molecule for incorporation into lipid-based nanoparticles, as it would not only improve their solubility but also increase the circulation time, availability and, potentially, targeting of tumors. In the current study, we compared the pharmacokinetics and tumor targeting of the bare EGFR kinase-targeting radiotracer SKI 212243 (SKI 243) with that of the same tracer embedded in liposomes. SKI 243 and liposomal SKI 243 are both taken up by tumor xenografts but liposomal SKI 243 remained in the blood longer and consequently exhibited a 3- to 6-fold increase in uptake in the tumor among several other organs. © 2010 Elsevier B.V.
Keywords: controlled study; unclassified drug; human cell; nonhuman; drug targeting; positron emission tomography; mouse; epidermal growth factor receptor; animal experiment; tumor xenograft; blood; medical imaging; tumors; gefitinib; imaging; nanoparticles; nanoparticle; radioactive tracers; tracer; egfr; indium 111; drug binding; diseases; enzymes; lipophilicity; liposome; liposomes; circulation time; pharmacokinetics; epidermal growth factor receptor kinase inhibitor; phospholipids; drug delivery; lipid solubility; inhibitors; liposomal delivery; diagnostics; radio tracer; theraphy; ski 243 i 124; ski 243 i 131
Journal Title: Journal of Controlled Release
Volume: 149
Issue: 3
ISSN: 0168-3659
Publisher: Elsevier B.V.  
Date Published: 2011-02-10
Start Page: 292
End Page: 298
Language: English
DOI: 10.1016/j.jconrel.2010.10.024
PROVIDER: scopus
PUBMED: 21047536
PMCID: PMC4452957
DOI/URL:
Notes: --- - "Export Date: 23 June 2011" - "CODEN: JCREE" - "Source: Scopus"
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MSK Authors
  1. Mithat Gonen
    716 Gonen
  2. Athanasios Glekas
    11 Glekas
  3. Pat B Zanzonico
    246 Zanzonico
  4. Steven M Larson
    779 Larson
  5. Valerie Ann Longo
    30 Longo