Accumulation of Tc-99m HL91 in Tumor Hypoxia: In Vitro Cell Culture and In Vivo Tumor Model

腫瘤缺氧是造成放射治療及化學治療效果不佳的原因之一；在治療前，以不具侵入性缺氧造影檢查評估腫瘤缺氧範圍，進而可以預估病人的預後；因此本研究採用離體細胞及活體動物實驗，研究Tc-99mHL91(HL91)是否極具有潛力成為一個缺氧造影藥物。將人類肺癌細胞(A549)及鼠類肺癌細胞(LL2)在缺氧及有氧環境，個別進行實驗。以A549細胞及LL2細胞個別接種至小鼠右後大腿，並分成hydralazine給予組及PBS給予組，個別進行生物體分佈實驗，核醫造影檢查及自動放射攝影實驗。細胞結果顯示HL91在缺氧環境較有氧環境確實有明顯地放射活性增加。在小鼠活體實驗，發現hydralazine給予組較PBS給予組有顯著地HL91放射活性增加；在核醫造影檢查方面，結果亦是如此。至於腫瘤切片的自動放射攝影則證實組織染色切片為壞死處的放射活性為最低，而壞死處周圍缺氧細胞則有較高放射活性增加的表現。藉由本實驗結果，證實HL91造影的確是可以提供評估腫瘤缺氧範圍及嚴重程度的影像檢查之運用。

關鍵字

離體細胞實驗；活體動物實驗；核醫造影檢查；鎝－99m HL91 ；腫瘤缺氧

並列摘要

Hypoxic cells within a tumor can account, in part, for resistance to radiotherapy and chemotherapy. Indeed, the oxygenation status has been shown to be a prognostic marker for the outcome of therapy. The purpose of this study was to determine whether Tc-99m HL91 (HL91), a noninvasive imaging tracer, detects tumor hypoxia in vitro in cell culture and in vivo in a tumor model. Uptake of HL91 in vitro into human lung cancer cells (A549) and murine Lewis lung cancer cells (LL2) was investigated at oxygen concentrations of 20% O2 (normoxia), and 1% O2 (hypoxia). HL91 biodistribution was studied in four groups: severe combined immune deficiency (SCID) mice bearing A549 tumors, C57BL/6NCrj (B6) mice bearing LL2 tumors, SCID controls, and B6 controls. Accumulation of the tracer was compared between tumors treated with hydralazine or phosphate-buffered saline (PBS). Scintigraphic images were obtained for hydralazine-treated mice and PBS-treated mice in each of the four study groups. Autoradiography of tumor slices was also acquired. In vitro studies identified hypoxia-selective uptake of HL91, with significantly increased uptake in the hypoxic state than in the normoxic state. Biodistribution and scintigraphy showed increased HL91 uptake during tumor hypoxia at 0.5 hours, and there was progressively increased activity for up to 4 hours after tracer administration. HL91 accumulation in tumor hypoxia was markedly increased in mice treated with hydralazine compared with those treated with PBS. Autoradiography revealed high HL91 uptake in the peripheral areas around the necrotic regions of the tumor, which were identified by histologic examination. HL91 exhibits selectivity for tumor hypoxia both in vitro and in vivo and provides a successful imaging modality for the detection of tumor hypoxia in vivo.

並列關鍵字

in vitro ； in vivo ； scintigraphy ； Tc-99m HL91 ； tumor hypoxia

國際替代計量

Accumulation of Tc-99m HL91 in Tumor Hypoxia: In Vitro Cell Culture and In Vivo Tumor Model

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