Avik Som1,2, Ramesh Raliya3, Krishna Paranandi1, Rachel A High4, Nathan Reed3, Scott C Beeman1, Matthew Brandenburg1, Gail Sudlow1, Julie L Prior1, Walter Akers1,5, Annelise Y Mah-Som6, Lemoyne Habimana-Griffin1,2, Joel Garbow1, Joseph E Ippolito1,7, Mark D Pagel4, Pratim Biswas3, Samuel Achilefu1,2,8,9. 1. Mallinckrodt Institute of Radiology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA. 2. Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO 63130, USA. 3. Department of Energy, Environmental, Chemical Engineering, Washington University in St Louis, St Louis, MO 63130, USA. 4. Cancer Biology Graduate Interdisciplinary Program, University of Arizona Cancer Center, Tucson, AZ 54724, USA. 5. Department of Biochemistry & Biophysics, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA. 6. Center for In Vivo Imaging & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. 7. Department of Pediatrics, Division of Rheumatology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA. 8. Department of Genetics, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA. 9. Department of Medicine, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA.
Abstract
AIM: CaCO3 nanoparticles (nano-CaCO3) can neutralize the acidic pHe of solid tumors, but the lack of intrinsic imaging signal precludes noninvasive monitoring of pH-perturbation in tumor microenvironment. We aim to develop a theranostic version of nano-CaCO3 to noninvasively monitor pH modulation and subsequent tumor response. MATERIALS & METHODS: We synthesized ferromagnetic core coated with CaCO3 (magnetite CaCO3). Magnetic resonance imaging (MRI) was used to determine the biodistribution and pH modulation using murine fibrosarcoma and breast cancer models. RESULTS: Magnetite CaCO3-MRI imaging showed that nano-CaCO3 rapidly raised tumor pHe, followed by excessive tumor-associated acid production after its clearance. Continuous nano-CaCO3 infusion could inhibit metastasis. CONCLUSION: Nano-CaCO3 exposure induces tumor metabolic reprogramming that could account for the failure of previous intermittent pH-modulation strategies to achieve sustainable therapeutic effect.
AIM: CaCO3 nanoparticles (nano-CaCO3) can neutralize the acidic pHe of solid tumors, but the lack of intrinsic imaging signal precludes noninvasive monitoring of pH-perturbation in tumor microenvironment. We aim to develop a theranostic version of nano-CaCO3 to noninvasively monitor pH modulation and subsequent tumor response. MATERIALS & METHODS: We synthesized ferromagnetic core coated with CaCO3 (magnetite CaCO3). Magnetic resonance imaging (MRI) was used to determine the biodistribution and pH modulation using murinefibrosarcoma and breast cancer models. RESULTS: Magnetite CaCO3-MRI imaging showed that nano-CaCO3 rapidly raised tumorpHe, followed by excessive tumor-associated acid production after its clearance. Continuous nano-CaCO3 infusion could inhibit metastasis. CONCLUSION: Nano-CaCO3 exposure induces tumor metabolic reprogramming that could account for the failure of previous intermittent pH-modulation strategies to achieve sustainable therapeutic effect.
Authors: G Cavaletti; G Bogliun; L Marzorati; A Zincone; M Piatti; N Colombo; G Parma; A Lissoni; F Fei; S Cundari; C Zanna Journal: Neurology Date: 2003-11-11 Impact factor: 9.910
Authors: Paul J Akhenblit; Neale T Hanke; Alexander Gill; Daniel O Persky; Christine M Howison; Mark D Pagel; Amanda F Baker Journal: Mol Imaging Date: 2016-05-02 Impact factor: 4.488