This study aimed to develop a PET imaging agent of angiomotin (AMOT) expression, a potential biomarker of functional tissue regeneration in post-ischaemic conditions.

Methods: Hindlimb ischaemia was induced by ligature and resection of the right femoral artery in mice, and clinical score and limb perfusion were evaluated up to 30 days after surgery. AMOT expression was evaluated by histology and Western blot analysis. NODAGA-conjugates of AMOT ligand, sCD146, were designed, synthesised and radiolabelled with gallium-68. ⁶⁸Ga-sCD146 microPET/CT imaging was performed from day 1 to day 30 after ischaemia. ⁶⁸Ga-sCD146 specificity for AMOT was evaluated by autoradiography.

Results: Immunohistochemistry showed a significant endothelial overexpression of AMOT from day 5 up to day 10 in the ischaemic hindlimb. ⁶⁸Ga-sCD146 PET signal intensity correlated significantly with AMOT immunohistochemistry evaluation. ⁶⁸Ga-sCD146 PET imaging showed a significant uptake in the ischaemic hindlimb from day 2 to day 15, peaking on day 5 (ipsi/contralateral ratio = 2.4 ± 1.3, P = 0.0005) and significantly decreased after pharmacological blocking (62.57 ± 11% decrease in PET signal P = 0.032). Finally, we observed a significant correlation between day 5 ⁶⁸Ga-sCD146 PET signal intensity and clinical recovery (day 28) or hindlimb perfusion recovery (day 30).

Conclusions: This work reports for the first time an early and sustained increase in AMOT expression after hindlimb ischaemia in mice. We therefore developed an AMOT-targeting imaging agent, ⁶⁸Ga-sCD146, and showed its specific uptake up to 21 days after ischaemic hindlimb using microPET imaging. Correlation of early post-ischaemic PET signal with both delayed perfusion recovery and clinical outcome allows us to postulate that ⁶⁸Ga-sCD146 represents a promising radiotracer for tissue angiogenesis assessment.

Keywords: angiomotin, ischaemia, sCD146, Gallium, angiogenesis.

这项研究的目的是开发血管生成抑制素（AMOT）表达的PET成像剂，血管生成素是在局部缺血后功能性组织再生的潜在生物标记。

方法：结扎小鼠右股动脉并切除后引起后肢缺血，并在术后30天评估其临床评分和肢体灌注。通过组织学和蛋白质印迹分析评估AMOT表达。设计，合成了AMOT配体sCD146的NODAGA-缀合物，并用68镓进行了放射性标记。缺血后第1天至第30天进行⁶⁸ Ga-sCD146 microPET / CT成像。通过放射自显影评价⁶⁸ Ga-sCD146对AMOT的特异性。

结果：免疫组织化学显示缺血后肢从第5天到第10天，AMOT的内皮表达显着升高。⁶⁸ Ga-sCD146 PET信号强度与AMOT免疫组织化学评估显着相关。⁶⁸ Ga-sCD146 PET成像显示从第2天到第15天缺血后肢的摄取显着，在第5天达到峰值（ipsi /对侧比= 2.4±1.3，P = 0.0005），并且在药理学阻断后显着下降（62.57±11％）降低PET信号P = 0.032）。最后，我们观察到第5天⁶⁸ Ga-sCD146 PET信号强度与临床恢复（第28天）或后肢灌注恢复（第30天）之间存在显着相关性。

结论：这项工作首次报告了小鼠后肢缺血后AMOT表达的早期和持续增加。因此，我们开发了一种靶向AMOT的显像剂⁶⁸ Ga-sCD146，并使用microPET显像显示了缺血后肢长达21天的特异性摄取。早期缺血后PET信号与延迟灌注恢复和临床结果的相关性使我们推测⁶⁸ Ga-sCD146代表了组织血管生成评估的有希望的放射性示踪剂。

关键词：血管动蛋白，缺血，sCD146，镓，血管生成。