Longitudinal Preclinical Imaging Characterizes Extracellular Drug Accumulation After Radiation Therapy in the Healthy and Leukemic Bone Marrow Vascular Microenvironment

Brooks, Jamison; Zuro, Darren; Song, Joo Y.; Madabushi, Srideshikan Sargur; Sanchez, James F.; Guha, Chandan; Kortylewski, Marcin; Chen, Bihong T.; Gupta, Kalpna; Storme, Guy; Song, Hui

doi:10.1016/j.ijrobp.2021.10.146

Cited by 4 publications

(2 citation statements)

References 37 publications

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“…To the best of our knowledge, this is the first study that investigated the patient’s extremities reproducibility in TMI/TMLI treatments. We think that these technical data regarding patient positioning are of current significance, particularly as new preclinical advancements in TMI/TMLI require implementation into clinical studies [ 24 , 25 ]. Our results demonstrated that careful consideration should be posed when deciding the immobilization method to use for the extremities.…”

Section: Discussionmentioning

confidence: 99%

Impact of the Extremities Positioning on the Set-Up Reproducibility for the Total Marrow Irradiation Treatment

et al. 2023

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Total marrow (lymph node) irradiation (TMI/TMLI) delivery requires more time than standard radiotherapy treatments. The patient’s extremities, through the joints, can experience large movements. The reproducibility of TMI/TMLI patients’ extremities was evaluated to find the best positioning and reduce unwanted movements. Eighty TMI/TMLI patients were selected (2013–2022). During treatment, a cone-beam computed tomography (CBCT) was performed for each isocenter to reposition the patient. CBCT-CT pairs were evaluated considering: (i) online vector shift (OVS) that matched the two series; (ii) residual vector shift (RVS) to reposition the patient’s extremities; (iii) qualitative agreement (range 1–5). Patients were subdivided into (i) arms either leaning on the frame or above the body; (ii) with or without a personal cushion for foot positioning. The Mann-Whitney test was considered (p < 0.05 significant). Six-hundred-twenty-nine CBCTs were analyzed. The median OVS was 4.0 mm, with only 1.6% of cases ranked < 3, and 24% of RVS > 10 mm. Arms leaning on the frame had significantly smaller RVS than above the body (median: 8.0 mm/6.0 mm, p < 0.05). Using a personal cushion for the feet significantly improved the RVS than without cushions (median: 8.5 mm/1.8 mm, p < 0.01). The role and experience of the radiotherapy team are fundamental to optimizing the TMI/TMLI patient setup.

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Section: Discussionmentioning

confidence: 99%

Impact of the Extremities Positioning on the Set-Up Reproducibility for the Total Marrow Irradiation Treatment

et al. 2023

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“…The MPM imaging using cranial window was carried out on SS mice according to a previous published study ( 24 ). Briefly, the day before microscopy imaging, a custom titanium head plate with an inner diameter of 8 mm was affixed directly on the frontal bone region of calvarium using Pearson PQ glass ionomer cement.…”

Section: Methodsmentioning

confidence: 99%

Development and characterization of a preclinical total marrow irradiation conditioning-based bone marrow transplant model for sickle cell disease

et al. 2022

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Sickle cell disease (SCD) is a serious global health problem, and currently, the only curative option is hematopoietic stem cell transplant (HCT). However, myeloablative total body irradiation (TBI)-based HCT is associated with high mortality/morbidity in SCD patients. Therefore, reduced-intensity (2–4 Gy) total body radiation (TBI) is currently used as a conditioning regimen resulting in mixed chimerism with the rescue of the SCD disease characteristic features. However, donor chimerism gradually reduces in a few years, resulting in a relapse of the SCD features, and organ toxicities remained the primary concern for long-term survivors. Targeted marrow irradiation (TMI) is a novel technique developed to deliver radiation to the desired target while sparing vital organs and is successfully used for HCT in refractory/relapsed patients with leukemia. However, it is unknown if TMI will be an effective treatment for a hematological disorder like SCD without adverse effects seen on TBI. Therefore, we examined preclinical feasibility to determine the tolerated dose escalation, its impact on donor engraftment, and reduction in organ damage using our recently developed TMI in the humanized homozygous Berkley SCD mouse model (SS). We show that dose-escalated TMI (8:2) (8 Gy to the bone marrow and 2 Gy to the rest of the body) is tolerated with reduced organ pathology compared with TBI (4:4)-treated mice. Furthermore, with increased SCD control (AA) mice (25 million) donor BM cells, TMI (8:2)-treated mice show successful long-term engraftment while engraftment failed in TBI (2:2)-treated mice. We further evaluated the benefit of dose-escalated TMI and donor cell engraftment in alleviating SCD features. The donor engraftment in SCD mice completely rescues SCD disease features including recovery in RBCs, hematocrit, platelets, and reduced reticulocytes. Moreover, two-photon microscopy imaging of skull BM of transplanted SCD mice shows reduced vessel density and leakiness compared to untreated control SCD mice, indicating vascular recovery post-BMT.

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Characterization of Microcirculatory Endothelial Functions in a D-Galactose-Induced Aging Model

Li,

He,

Zhang

et al. 2024

Preprint

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Longitudinal Preclinical Imaging Characterizes Extracellular Drug Accumulation After Radiation Therapy in the Healthy and Leukemic Bone Marrow Vascular Microenvironment

Cited by 4 publications

References 37 publications

Impact of the Extremities Positioning on the Set-Up Reproducibility for the Total Marrow Irradiation Treatment

Impact of the Extremities Positioning on the Set-Up Reproducibility for the Total Marrow Irradiation Treatment

Development and characterization of a preclinical total marrow irradiation conditioning-based bone marrow transplant model for sickle cell disease

Characterization of Microcirculatory Endothelial Functions in a D-Galactose-Induced Aging Model

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