Preclinical Evaluation of the Hsp70 Peptide Tracer TPP-PEG24 -DFO[89 Zr] for Tumor-Specific PET/CT Imaging

Cancer Research
Stefan StanglGabriele Multhoff

Abstract

High precision in vivo PET/CT imaging of solid tumors improves diagnostic credibility and clinical outcome of patients. An epitope of the oligomerization domain of Hsp70 is exclusively exposed on the membrane of a large variety of tumor types, but not on normal cells, and thus provides a universal tumor-specific target. Here we developed a novel PET tracer TPP-PEG24-DFO[89Zr] based on the tumor cell-penetrating peptide probe TPP, which specifically recognizes membrane Hsp70 (mHsp70) on tumor cells. The implemented PEG24 moiety supported tracer stability and improved biodistribution characteristics in vivo The Kd of the tracer ranged in the low nanomolar range (18.9 ± 11.3 nmol/L). Fluorescein isothiocyanate (FITC)-labeled derivatives TPP-[FITC] and TPP-PEG24-[FITC] revealed comparable and specific binding to mHsp70-positive 4T1, 4T1+, a derivative of the 4T1 cell line sorted for high Hsp70 expression, and CT26 tumor cells, but not to mHsp70-negative normal fibroblasts. The rapid internalization kinetics of mHsp70 into the cytosol and the favorable biodistribution of the peptide-based tracer TPP-PEG24-DFO[89Zr] in vivo enabled a tumor-specific accumulation with a high tumor-to-background contrast and renal body clearance. The tu...Continue Reading

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Citations

Dec 13, 2019·ChemMedChem·Lisa RusselliCalogero D'Alessandria
Feb 11, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Shulei ZhuWei Lu
Jul 3, 2020·Journal of Clinical Medicine·Francesco CappelloAlberto Jl Macario
Aug 4, 2019·Cell Stress & Chaperones·Lukas SalvermoserGabriele Multhoff
Mar 7, 2020·Pharmaceutics·Rebecca E Taylor, Maliha Zahid
Dec 10, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Hsin-Yu FangMichael Quante
Jan 11, 2022·EJNMMI Research·Sabrina MarcazzanMichael Quante

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