Sluka Pavel, Ackermann Uwe, Rigopoulos Angela, Wardan Hady, Pezaro Carmel, Burvenich Ingrid J G, Scott Andrew M, Davis Ian D
Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.
Department of Molecular Imaging and Therapy, Austin Hospital, Heidelberg, VIC, Australia.
World J Nucl Med. 2024 Jun 18;23(3):153-160. doi: 10.1055/s-0044-1786518. eCollection 2024 Sep.
Conventional imaging of cancer with modalities such as computed tomography or magnetic resonance imaging provides little information about the underlying biology of the cancer and consequently little guidance for systemic treatment choices. Accurate identification of aggressive cancers or those that are likely to respond to specific treatment regimens would allow more precisely tailored treatments to be used. The expression of the estrogen receptor α subunit is associated with a more aggressive phenotype, with a greater propensity to metastasize. We aimed to characterize the binding properties of an F-estradiol positron emission tomography (PET) tracer in its ability to bind to the α and β forms of estrogen receptors in vitro and confirmed its binding to estrogen receptor α in vivo. The F-estradiol PET tracer was synthesized and its quality confirmed by high-performance liquid chromatography. Binding of the tracer was assessed in vitro by saturation and competitive binding studies to HEK293T cells transfected with estrogen receptor α ( ) and/or estrogen receptor β ( ). Binding of the tracer to estrogen receptor α in vivo was assessed by imaging of uptake of the tracer into MCF7 xenografts in BALB/c nu/nu mice. The F-estradiol PET tracer bound with high affinity (94 nM) to estrogen receptor α, with negligible binding to estrogen receptor β. Uptake of the tracer was observed in MCF7 xenografts, which almost exclusively express estrogen receptor α. F-estradiol PET tracer binds in vitro with high specificity to the estrogen receptor α isoform, with minimal binding to estrogen receptor β. This may help distinguish human cancers with biological dependence on estrogen receptor subtypes.
使用计算机断层扫描或磁共振成像等方式对癌症进行传统成像，只能提供关于癌症潜在生物学特性的极少信息，因此对于全身治疗方案的选择几乎没有指导作用。准确识别侵袭性癌症或可能对特定治疗方案有反应的癌症，将有助于采用更精准的个性化治疗。雌激素受体α亚基的表达与更具侵袭性的表型相关，转移倾向更大。我们旨在表征一种氟雌二醇正电子发射断层扫描（PET）示踪剂的结合特性，即其在体外与雌激素受体α和β形式结合的能力，并在体内证实其与雌激素受体α的结合。
合成了氟雌二醇PET示踪剂，并通过高效液相色谱法确认其质量。通过对转染了雌激素受体α（ ）和/或雌激素受体β（ ）的HEK293T细胞进行饱和结合和竞争结合研究，在体外评估示踪剂的结合情况。通过对BALB/c nu/nu小鼠体内MCF7异种移植瘤摄取示踪剂的成像，评估示踪剂在体内与雌激素受体α的结合情况。
氟雌二醇PET示踪剂以高亲和力（94 nM）与雌激素受体α结合，与雌激素受体β的结合可忽略不计。在几乎只表达雌激素受体α的MCF7异种移植瘤中观察到了示踪剂的摄取。
氟雌二醇PET示踪剂在体外与雌激素受体α亚型具有高特异性结合，与雌激素受体β的结合极少。这可能有助于区分对雌激素受体亚型有生物学依赖性的人类癌症。
