Characterization of Spontaneous Bone Marrow Recovery after Sublethal Total Body Irradiation: Importance of the Osteoblastic/Adipocytic Balance

Many studies have already examined the hematopoietic recovery after irradiation but paid with very little attention to the bone marrow microenvironment. Nonetheless previous studies in a murine model of reversible radio-induced bone marrow aplasia have shown a significant increase in alkaline phosphatase activity (ALP) prior to hematopoietic regeneration. This increase in ALP activity was not due to cell proliferation but could be attributed to modifications of the properties of mesenchymal stem cells (MSC). We thus undertook a study to assess the kinetics of the evolution of MSC correlated to their hematopoietic supportive capacities in mice treated with sub lethal total body irradiation. In our study, colony-forming units – fibroblasts (CFU-Fs) assay showed a significant MSC rate increase in irradiated bone marrows. CFU-Fs colonies still possessed differentiation capacities of MSC but colonies from mice sacrificed 3 days after irradiation displayed high rates of ALP activity and a transient increase in osteoblastic markers expression while pparγ and neuropilin-1 decreased. Hematopoietic supportive capacities of CFU-Fs were also modified: as compared to controls, irradiated CFU-Fs significantly increased the proliferation rate of hematopoietic precursors and accelerated the differentiation toward the granulocytic lineage. Our data provide the first evidence of the key role exerted by the balance between osteoblasts and adipocytes in spontaneous bone marrow regeneration. First, (pre)osteoblast differentiation from MSC stimulated hematopoietic precursor's proliferation and granulopoietic regeneration. Then, in a second time (pre)osteoblasts progressively disappeared in favour of adipocytic cells which down regulated the proliferation and granulocytic differentiation and then contributed to a return to pre-irradiation conditions

Organs dosimetry in targeted radionuclide therapy

The objective of this study is to assess the patients' effective and organ dose during theranostic applications in Kuwait. In total, eighteen adults' patients were conducted nuclear medicine procedures with 177Lu Dotatate for theranostic purpose in Kuwait Cancer control center (KCCC), Kuwait. Medium energy collimator (MEC) (208 keV Scatter 26% better than 113 keV Scatter 60%) was utilized to obtain scans in definite time intervals ranged from one to 2 h (before voiding), 6:00, 24:00, 48:00, 72:00 h. Patients, tissue and organ radiation doses were computed utilizing OLINDA/EXM Software. The average radiation effective dose (in mSv/MBq) for bladder, liver, and both kidneys (left & right), were 0.36, 0.08, 0.61 & 0.60. The range of the effective dose was from 0.55 mSv to 7.7 mSv. The acquired scans using 177Lu were delivered diagnostic findings. The patients’ effective dose is lower compared to the previous studies. Variation is attributed to the departmental protocol and administered activity. The values of the mean organ dose were comparable and lower than previously published studies. Different organs have different level of doses, which may affected by the presence of the metastatic tumors in the entire organ. © 2021 Elsevier Lt