Dell'Oglio Paolo, van Willigen Danny M, van Oosterom Matthias N, Bauwens Kevin, Hensbergen Fabian, Welling Mick M, van der Stadt Huijbert, Bekers Elise, Pool Martin, van Leeuwen Pim, Maurer Tobias, van Leeuwen Fijs W B, Buckle Tessa
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.
Department of Urology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
EJNMMI Res. 2022 Mar 7;12(1):14. doi: 10.1186/s13550-022-00886-y.
With the rise of prostate-specific membrane antigen (PSMA) radioguided surgery, which is performed using a microdosing regime, demand for visual target confirmation via fluorescence guidance is growing. While proven very effective for radiotracers, microdosing approaches the detection limit for fluorescence imaging. Thus, utility will be highly dependent on the tracer performance, the sensitivity of the fluorescence camera used, and the degree of background signal. Using a porcine model the ability to perform robot-assisted radical prostatectomy under fluorescence guidance using the bimodal or rather hybrid PSMA tracer (Tc-EuK-(SO)Cy5-mas) was studied, while employing the tracer in a microdosing regime. This was followed by ex vivo evaluation in surgical specimens obtained from prostate cancer patients.
T and T were reached at 85 min and 390 min, in, respectively, blood and urine. Surgical fluorescence imaging allowed visualization of the prostate gland based on the basal PSMA-expression in porcine prostate. Together, in vivo visualization of the prostate and urinary excretion suggests at least an interval of > 7 h between tracer administration and surgery. Confocal microscopy of excised tissues confirmed tracer uptake in kidney and prostate, which was confirmed with PSMA IHC. No fluorescence was detected in other excised tissues. Tumor identification based on ex vivo fluorescence imaging of human prostate cancer specimens correlated with PSMA IHC.
Intraoperative PSMA-mediated fluorescence imaging with a microdosing approach was shown to be feasible. Furthermore, EuK-(SO)Cy5-mas allowed tumor identification in human prostate samples, underlining the translational potential of this novel tracer. Trial registration Approval for use of biological material for research purposes was provided by the Translational Research Board of the Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital (NKI-AvL) under reference IRBm19-273 (22/10/2019).
随着使用微量给药方案进行的前列腺特异性膜抗原（PSMA）放射性引导手术的兴起，通过荧光引导进行视觉目标确认的需求日益增长。虽然已证明对放射性示踪剂非常有效，但微量给药接近荧光成像的检测极限。因此，其效用将高度依赖于示踪剂性能、所用荧光相机的灵敏度以及背景信号程度。使用猪模型，研究了在微量给药方案中使用双峰或更确切地说是混合PSMA示踪剂（Tc-EuK-(SO)Cy5-mas）在荧光引导下进行机器人辅助根治性前列腺切除术的能力，随后对从前列腺癌患者获得的手术标本进行体外评估。
血液和尿液中分别在85分钟和390分钟达到T和T。手术荧光成像基于猪前列腺中的基础PSMA表达实现了前列腺的可视化。总体而言，前列腺的体内可视化和尿液排泄表明示踪剂给药与手术之间至少间隔>7小时。切除组织的共聚焦显微镜检查证实了肾脏和前列腺中示踪剂的摄取，这通过PSMA免疫组化得到证实。在其他切除组织中未检测到荧光。基于人前列腺癌标本体外荧光成像的肿瘤识别与PSMA免疫组化相关。
术中采用微量给药方法的PSMA介导的荧光成像被证明是可行的。此外，EuK-(SO)Cy5-mas能够在人前列腺样本中识别肿瘤，突出了这种新型示踪剂的转化潜力。试验注册 荷兰癌症研究所-安东尼·范·列文虎克医院（NKI-AvL）的转化研究委员会根据参考编号IRBm19-273（2019年10月22日）批准将生物材料用于研究目的。
