Phelps Tim E, Roy Jyoti, Green Michael V, Seidel Jurgen, Baidoo Kwamena E, Adler Stephen, Edmondson Elijah F, Butcher Donna, Matta Jennifer L, Ton Anita T, Wong Karen, Huang Shan, Ren Ling, LeBlanc Amy K, Choyke Peter L, Jagoda Elaine M
Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Clinical Research Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Bethesda, Maryland, USA.
Cancer Biother Radiopharm. 2021 Mar;36(2):133-142. doi: 10.1089/cbr.2020.4068. Epub 2021 Feb 25.
Patients with osteoblastic bone metastases are candidates for radium-223 (RaCl) therapy and may undergo sodium fluoride-18 (F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. F-NaF has been shown to predict RaCl uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of F-NaF and RaCl in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. F-NaF and RaCl were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. F and Ra accumulated in proportional amounts in whole Hu09-H3 tumors ( = 0.82) and in microcalcified regions within these tumors ( = 0.87). Intratumor distributions of F and Ra were spatially congruent in these microcalcified regions. F-NaF and RaCl uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of F is predictive of Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered Ra dose and therapeutic effect.
成骨性骨转移患者是镭-223（RaCl）治疗的候选对象，可能会接受氟化钠-18（F-NaF）正电子发射断层扫描-计算机断层扫描成像以识别骨病变。F-NaF已被证明可预测RaCl摄取，但这两种药物在肿瘤内的分布仍不清楚。在本研究中，作者在宏观和微观水平评估了F-NaF和RaCl在Hu09-H3人骨肉瘤小鼠异种移植瘤中的空间分布和相对摄取情况，以更好地量化它们之间的相关性。将F-NaF和RaCl共同注射到Hu09-H3异种移植瘤严重联合免疫缺陷小鼠体内。通过生物分布确定肿瘤含量，并通过正电子发射断层扫描、单光子发射计算机断层扫描和计算机断层扫描成像进行可视化。通过肿瘤组织切片的定量放射自显影观察肿瘤内分布，并与相同或相邻切片的组织学进行比较。F和Ra在整个Hu09-H3肿瘤中以成比例的量积累（=0.82），并在这些肿瘤内的微钙化区域中积累（=0.87）。在这些微钙化区域中，F和Ra的肿瘤内分布在空间上是一致的。在Hu09-H3异种移植瘤异质性分布的微钙化区域中，F-NaF和RaCl摄取密切相关，因此，F的肿瘤积累可预测Ra的积累。Hu09-H3异种移植瘤似乎具有转移性骨病患者中发现的某些组织病理学特征，可能有助于阐明给予的Ra剂量与治疗效果之间的关系。
