en Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;"><span style="font-size:10pt"><span style="text-justify:newspaper"><span style="text-kashida-space:50%"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Background:</span></span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">High Altitude Polycythemia (HAPC) is a chronic hypoxia-related disorder characterized by excessive erythrocytosis, hypercoagulability, and organ dysfunction. Hydroxyurea (HU) is used clinically but is limited by systemic toxicity and suboptimal targeting. This study aimed to evaluate the therapeutic efficacy and biodistribution of a radiopharmaceutical platform based on poly(lactic-co-glycolic acid) nanoparticles loaded with hydroxyurea (HU-PLGA-NPs) in an experimental HAPC model. </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Materials and Methods: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">Sixty male Sprague&ndash;Dawley rats with hypobaric hypoxia-induced HAPC were randomized into three groups: HU-PLGA-NPs, conventional HU, and supportive treatment. Nanoparticles were radiolabeled with technetium-99m to assess in vivo biodistribution using SPECT/CT imaging. Hematological parameters, coagulation indices, hemorheology, immune markers, bone marrow apoptosis, and liver and renal function were evaluated over 12 weeks. </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Results: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">HU-PLGA-NP treatment significantly reduced hemoglobin, hematocrit, blood viscosity, and coagulation abnormalities compared with conventional HU and supportive therapy (p<0.05). Imaging and biodistribution studies demonstrated preferential accumulation in bone marrow and spleen. Improved immune parameters and reduced hepatic and renal toxicity were observed in the nanoparticle group. </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Conclusions: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">The HU-PLGA-NP radiopharmaceutical platform enhances therapeutic efficacy and targeting while reducing systemic toxicity in HAPC, representing a promising strategy for precision treatment.</span></span></span></span></span></span></span></span></span></div> Hydroxyurea, PLGA nanoparticles, radiopharmaceutical platform, technetium-99m, high altitude polycythemia, biodistribution, liver function, coagulation indices. 1007 1015 http://ijrr.com/browse.php?a_code=A-10-1-1609&slc_lang=en&sid=1 J. Nie fcmlnj@163.com 7900319475328460034870 7900319475328460034870 Yes School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China D. Wang 7900319475328460034871 7900319475328460034871 No School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China M.J. Li 7900319475328460034872 7900319475328460034872 No College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China