Jamison Brooks1, Darren Zuro1, Joo Y Song2, Srideshikan Sargur Madabushi3, James F Sanchez4, Chandan Guha5, Marcin Kortylewski6, Bihong T Chen7, Kalpna Gupta8, Guy Storme9, Jerry Froelich10, Susanta K Hui11. 1. Department of Radiation Oncology, City of Hope, Duarte, California; Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota. 2. Department of Pathology, City of Hope, Duarte, California. 3. Department of Radiation Oncology, City of Hope, Duarte, California. 4. Beckman Research Institute of City of Hope, Duarte, California. 5. Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York. 6. Department of Immuno-Oncology, Beckman Research Institute, City of Hope, Duarte, California. 7. Department of Diagnostic Radiology, City of Hope Medical Center, Duarte, California. 8. Hematology/Oncology, Department of Medicine, University of California, Irvine and Southern California Institute for Research and Education, VA Medical Center, North Hills, California; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota. 9. Department of Radiotherapy, UZ Brussel, Jette, Belgium. 10. Department of Radiology, University of Minnesota, Minneapolis, Minnesota. 11. Department of Radiation Oncology, City of Hope, Duarte, California; Beckman Research Institute of City of Hope, Duarte, California. Electronic address: shui@coh.org.
Abstract
PURPOSE: Recent initial findings suggest that radiation therapy improves blood perfusion and cellular chemotherapy uptake in mice with leukemia. However, the ability of radiation therapy to influence drug accumulation in the extracellular bone marrow tissue is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton microscopy (L-QMPM) to characterize the bone marrow vasculature (BMV) and drug accumulation in the extracellular bone marrow tissue before and after radiation therapy in mice bearing leukemia. METHODS AND MATERIALS: We developed a longitudinal window implant for L-QMPM imaging of the calvarium BMV before, 2 days after, and 5 days after total body irradiation (TBI). Live time-lapsed images of a fluorescent drug surrogate were used to obtain measurements, including tissue wash-in slope (WIStissue) to measure extracellular drug accumulation. We performed L-QMPM imaging on healthy C57BL/6 (WT) mice, as well as mice bearing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). RESULTS: Implants had no effects on calvarium dose, and parameters for wild-type untreated mice were stable during imaging. We observed decreased vessel diameter, vessel blood flow, and WIStissue with the onset of AML and ALL. Two to 10 Gy TBI increased WIStissue and vessel diameter 2 days after radiation therapy in all 3 groups of mice and increased single-vessel blood flow in mice bearing ALL and AML. Increased WIStissue was observed 5 days after 10 Gy TBI or 4 Gy split-dose TBI (2 treatments of 2 Gy spaced 3 days apart). CONCLUSIONS: L-QMPM provides stable functional assessments of the BMV. Nonmyeloablative and myeloablative TBI increases extracellular drug accumulation in the leukemic bone marrow 2 to 5 days posttreatment, likely through improved blood perfusion and drug exchange from the BMV to the extravascular tissue. Our data show that neo-adjuvant TBI at doses from 2 Gy to 10 Gy conditions the BMV to improve drug transport to the bone marrow.
PURPOSE: Recent initial findings suggest that radiation therapy improves blood perfusion and cellular chemotherapy uptake in mice with leukemia. However, the ability of radiation therapy to influence drug accumulation in the extracellular bone marrow tissue is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton microscopy (L-QMPM) to characterize the bone marrow vasculature (BMV) and drug accumulation in the extracellular bone marrow tissue before and after radiation therapy in mice bearing leukemia. METHODS AND MATERIALS: We developed a longitudinal window implant for L-QMPM imaging of the calvarium BMV before, 2 days after, and 5 days after total body irradiation (TBI). Live time-lapsed images of a fluorescent drug surrogate were used to obtain measurements, including tissue wash-in slope (WIStissue) to measure extracellular drug accumulation. We performed L-QMPM imaging on healthy C57BL/6 (WT) mice, as well as mice bearing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). RESULTS: Implants had no effects on calvarium dose, and parameters for wild-type untreated mice were stable during imaging. We observed decreased vessel diameter, vessel blood flow, and WIStissue with the onset of AML and ALL. Two to 10 Gy TBI increased WIStissue and vessel diameter 2 days after radiation therapy in all 3 groups of mice and increased single-vessel blood flow in mice bearing ALL and AML. Increased WIStissue was observed 5 days after 10 Gy TBI or 4 Gy split-dose TBI (2 treatments of 2 Gy spaced 3 days apart). CONCLUSIONS: L-QMPM provides stable functional assessments of the BMV. Nonmyeloablative and myeloablative TBI increases extracellular drug accumulation in the leukemic bone marrow 2 to 5 days posttreatment, likely through improved blood perfusion and drug exchange from the BMV to the extravascular tissue. Our data show that neo-adjuvant TBI at doses from 2 Gy to 10 Gy conditions the BMV to improve drug transport to the bone marrow.
Authors: Preetesh Jain; Hun Ju Lee; Wei Qiao; William Wierda; Ohad Benjamini; Jan Burger; Alessandra Ferrajoli; Zeev Estrov; Hagop Kantarjian; Michael Keating; Susan O'Brien Journal: Cancer Date: 2014-07-15 Impact factor: 6.860
Authors: T M Moehler; H Hawighorst; K Neben; G Egerer; J Hillengass; R Max; A Benner; A D Ho; G van Kaick; H Goldschmidt Journal: Int J Cancer Date: 2001-09 Impact factor: 7.396
Authors: Esther A Kleibeuker; Emmanouil Fokas; Philip D Allen; Veerle Kersemans; Arjan W Griffioen; John Beech; Jaehong H Im; Sean C Smart; Kitty C Castricum; Jaap van den Berg; Iris A Schulkens; Sally A Hill; Adrian L Harris; Ben J Slotman; Henk M Verheul; Ruth J Muschel; Victor L Thijssen Journal: Oncotarget Date: 2016-11-22
Authors: Yolla Haibe; Malek Kreidieh; Hiba El Hajj; Ibrahim Khalifeh; Deborah Mukherji; Sally Temraz; Ali Shamseddine Journal: Front Oncol Date: 2020-02-27 Impact factor: 6.244
Authors: Srideshikan Sargur Madabushi; Raghda Fouda; Hemendra Ghimire; Amr M H Abdelhamid; Ji Eun Lim; Paresh Vishwasrao; Stacy Kiven; Jamison Brooks; Darren Zuro; Joseph Rosenthal; Chandan Guha; Kalpna Gupta; Susanta K Hui Journal: Front Oncol Date: 2022-09-06 Impact factor: 5.738