PURPOSE: To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastoma patient-derived xenografts. METHODS: We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (f = extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice. In vivo microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (Vu,tumor) in neuroblastoma. RESULTS: HPBCD (10% w/v) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (f = 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. Vu,tumor values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38. CONCLUSIONS: The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.
PURPOSE: To develop a reproducible microdialysis-tumor homogenate method for the study of the intratumor distribution of a highly hydrophobic anticancer drug (SN-38; 7-ethyl-10-hydroxycamptothecin) in neuroblastomapatient-derived xenografts. METHODS: We studied the nonspecific binding of SN-38 to the microdialysis tubing in the presence of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the perfusate. We calibrated the microdialysis probes by the zero flow rate (ZFR) method and calculated the enhancement factor (f = extrapolated SN-38 concentration at the ZFR / SN-38 concentration in the dialysed solution) of HPBCD. We characterized the extravasation of HPBCD to tumors engrafted in mice. In vivo microdialysis and terminal homogenate data at the steady state (subcutaneous pump infusions) were used to calculate the volume of distribution of unbound SN-38 (Vu,tumor) in neuroblastoma. RESULTS:HPBCD (10% w/v) in the perfusate prevented the nonspecific binding of SN-38 to the microdialysis probe and enhanced SN-38 recovery (f = 1.86). The extravasation of HPBCD in the tumor during microdialysis was lower than 1%. Vu,tumor values were above 3 mL/g tumor for both neuroblastoma models and suggested efficient cellular penetration of SN-38. CONCLUSIONS: The method contributes to overcome the limitations of the microdialysis technique in hydrophobic drugs and provides a powerful tool to characterize compartmental anticancer drug distribution in xenografts.
Authors: Paolo P Provenzano; Carlos Cuevas; Amy E Chang; Vikas K Goel; Daniel D Von Hoff; Sunil R Hingorani Journal: Cancer Cell Date: 2012-03-20 Impact factor: 31.743
Authors: Amanda Balboni Iniguez; Björn Stolte; Emily Jue Wang; Amy Saur Conway; Gabriela Alexe; Neekesh V Dharia; Nicholas Kwiatkowski; Tinghu Zhang; Brian J Abraham; Jaume Mora; Peter Kalev; Alan Leggett; Dipanjan Chowdhury; Cyril H Benes; Richard A Young; Nathanael S Gray; Kimberly Stegmaier Journal: Cancer Cell Date: 2018-01-18 Impact factor: 31.743
Authors: Carles Monterrubio; Sonia Paco; Nagore G Olaciregui; Guillem Pascual-Pasto; Monica Vila-Ubach; Maria Cuadrado-Vilanova; M Mar Ferrandiz; Helena Castillo-Ecija; Romina Glisoni; Nataliya Kuplennik; Achim Jungbluth; Carmen de Torres; Cinzia Lavarino; N K V Cheung; Jaume Mora; Alejandro Sosnik; Angel M Carcaboso Journal: J Control Release Date: 2017-04-12 Impact factor: 9.776