Department of Radiology, University of California San Diego, La Jolla, California.
Department of Pharmacology, University of California San Diego, La Jolla, California.
J Nucl Med. 2021 Aug 1;62(8):1146-1153. doi: 10.2967/jnumed.120.255273. Epub 2020 Dec 4.
Inflammation is associated with a range of serious human conditions, including autoimmune and cardiovascular diseases and cancer. The ability to image active inflammatory processes greatly enhances our ability to diagnose and treat these diseases at an early stage. We describe molecular compositions enabling sensitive and precise imaging of inflammatory hotspots in vivo. A functionalized nanoemulsion with a fluorocarbon-encapsulated radiometal chelate (FERM) was developed to serve as a platform for multimodal imaging probe development. The F-containing FERM nanoemulsion encapsulates Zr in the fluorous oil via a fluorinated hydroxamic acid chelate. Simple mixing of the radiometal with the preformed aqueous nanoemulsion before use yields FERM, a stable in vivo cell tracer, enabling whole-body Zr PET and F MRI after a single intravenous injection. The FERM nanoemulsion was intrinsically taken up by phagocytic immune cells, particularly macrophages, with high specificity. FERM stability was demonstrated by a high correlation between the F and Zr content in the blood (correlation coefficient > 0.99). Image sensitivity at a low dose (37 kBq) was observed in a rodent model of acute infection. The versatility of FERM was further demonstrated in models of inflammatory bowel disease and 4T1 tumor. Multimodal detection using FERM yields robust whole-body lesion detection and leverages the strengths of combined PET and F MRI. The FERM nanoemulsion has scalable production and is potentially useful for precise diagnosis, stratification, and treatment monitoring of inflammatory diseases.
炎症与一系列严重的人类疾病有关，包括自身免疫性疾病、心血管疾病和癌症。能够对活跃的炎症过程进行成像，极大地提高了我们在早期诊断和治疗这些疾病的能力。我们描述了能够在体内敏感而精确地成像炎症热点的分子组成。开发了一种功能化的纳米乳液，其中包含氟碳包裹的放射性金属螯合物（FERM），作为用于多模式成像探针开发的平台。含氟的 FERM 纳米乳液通过氟化的羟肟酸螯合物将 Zr 封装在氟碳油中。在使用前，只需将放射性金属与预先形成的水性纳米乳液简单混合，即可得到 FERM，这是一种稳定的体内细胞示踪剂，在单次静脉注射后即可进行 Zr PET 和 F MRI 全身扫描。 FERM 纳米乳液被吞噬性免疫细胞（特别是巨噬细胞）高度特异性地摄取。FERM 的稳定性通过血液中 F 和 Zr 含量之间的高度相关性（相关系数>0.99）得到证明。在急性感染的啮齿动物模型中观察到低剂量（37 kBq）下的图像灵敏度。FERM 的多功能性在炎症性肠病和 4T1 肿瘤模型中得到了进一步证明。使用 FERM 进行多模式检测可实现强大的全身病变检测，并利用 PET 和 F MRI 的优势。FERM 纳米乳液具有可扩展的生产能力，对于炎症性疾病的精确诊断、分层和治疗监测可能具有重要意义。
