Multichannel Fluorescence Guided Surgery Tools Enabling Simultaneous Cancer Margin and Nerve Visualization in Prostatectomy
多通道荧光引导手术工具可在前列腺切除术中同时实现癌症边缘和神经可视化
基本信息
- 批准号:10619640
- 负责人:
- 金额:$ 61.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-10 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:Adverse effectsAffectAffinityAntigen TargetingBiodistributionCancer ControlCancer EtiologyCancer PatientCessation of lifeClinicalClinical MedicineCollaborationsColorContrast MediaDevelopmentDoseDose LimitingDrug KineticsFDA approvedFOLH1 geneFaceFluorescenceFutureGoalsImageImpotenceIncontinenceIntuitionLabelLeadLightMalignant NeoplasmsMalignant neoplasm of prostateMethodsMorbidity - disease rateNerveNerve PlexusNerve TissueNerve-Sparing ProstatectomyNude RatsOperating RoomsOperative Surgical ProceduresOutcomePatient-Focused OutcomesPatientsPharmacodynamicsPharmacology and ToxicologyPhase I Clinical TrialsPostoperative PeriodProstateProstate Cancer therapyProstatectomyProstaticQuality of lifeRobotRodentSafetySpecificitySurgeonSurgical marginsSystemTechnologyTimeTissuesToxic effectToxicologyTranslationsTumor TissueVisual AcuityVisualizationWaterWorkXenograft procedurecancer imagingchromophoreclinical translationclinically relevantcomorbiditycontrast imagingexperiencefallsfluorescence imagingfluorescence-guided surgeryfluorophoreimprovedmenmortalitynerve damagenoveloverexpressionpre-clinicalpreclinical safetypreservationprototyperobot assistancesmall moleculespared nervesurgery outcometooltumor
项目摘要
PROJECT SUMMARY
Prostate cancer is the most prevalent cancer in men and the second leading cause of cancer death. Prostatec-
tomy is one of the most common primary treatments for prostate cancer, where surgeons face two main goals:
prostate cancer cure and nerve preservation. However, with little visual acuity for nerve plexus recognition and
conclusive cancer delineation, ideal outcomes for patients continue to challenge even experienced surgeons.
Positive surgical margins and nerve damage occur in up to 21 and 60% of patients, respectively, resulting in
poor cancer control as well as incontinence and impotence severely affecting post-operative quality of life. No
clinically approved methods exist to enhance direct cancer or nerve plexus visualization intraoperatively. Thus,
technology to enable the direct visualization of cancer tissue and nerves simultaneously in real time would greatly
reduce associated comorbidities and significantly improve prostatectomy outcomes. Fluorescence Guided Sur-
gery (FGS) has successfully integrated into clinical medicine with only two FDA-approved fluorophores, providing
surgeons real-time visualization. FGS systems operate mainly at near infrared (NIR, 700-900 nm) wavelengths,
where tissue chromophore absorbance, autofluorescence and scatter fall to local minima, allowing high contrast
imaging at up to centimeter depths. A number of targeted NIR contrast agents are under development, including
nerve- and prostate-specific probes that together would provide an integrated FGS tool for prostatectomy. In the
US, >80% of prostatectomies are performed using robotic-assistance, where the da Vinci surgical robot (Intuitive
Surgical) is the most common and is equipped standard with a NIR fluorescence-imaging channel capable of
real-time visualization. Herein, we will collaborate with Drs. Jonathan Sorger (Intuitive Surgical) and Scott Davis
(Dartmouth) to develop a multicolor FGS solution for prostatectomy that highlights both cancer and nerve tissues
to improve patient outcomes. Prostate specific membrane antigen (PSMA) is overexpressed in the majority of
prostate cancers making it a promising target for prostate cancer imaging. A handful of molecules have shown
high affinity for PSMA following labeling, which have been extensively investigated, where 800 nm PSMA tar-
geted IS-002 has successfully completed Phase I clinical trials sponsored by Intuitive Surgical. Herein, we will
develop a NIR, spectrally-distinct, nerve-specific fluorophore for co-administration with PSMA-targeted IS-002 to
bring this new FGS paradigm to prostate cancer patients. In exciting preliminary work, our team has synthesized
NIR nerve-specific fluorophores that can be imaged with clinical FGS systems. Herein, 700 nm NIR nerve-spe-
cific probes will be synthetically tuned for co-administration with PSMA-specific 800 nm IS-002 and validated for
future translation to guided prostatectomy. These goals will be accomplished through the following specific aims:
Aim 1: Synthesize 700 nm NIR nerve-specific FGS probes. Aim 2: Quantify preclinical pharmacology and toxi-
cology of NIR nerve-specific probes co-administered with IS-002. Aim 3: Select a lead nerve-specific probe for
co-administration with IS-002 through demonstration of nerve- and prostate cancer-specific contrast.
项目概要
前列腺癌是男性中最常见的癌症,也是癌症死亡的第二大原因。前列腺癌-
tomy 是前列腺癌最常见的主要治疗方法之一,外科医生面临两个主要目标:
前列腺癌治愈和神经保留。然而,神经丛识别和识别能力较差
即使对于经验丰富的外科医生来说,确定性的癌症描绘、患者的理想结果仍然是一个挑战。
高达 21% 和 60% 的患者出现手术切缘阳性和神经损伤,从而导致
癌症控制不佳以及失禁和阳痿严重影响术后生活质量。不
存在临床批准的方法来增强术中直接癌症或神经丛的可视化。因此,
能够同时实时直接可视化癌症组织和神经的技术将极大地促进
减少相关合并症并显着改善前列腺切除术的结果。荧光引导环绕
gery (FGS) 已成功融入临床医学,仅使用两种 FDA 批准的荧光团,提供
外科医生实时可视化。 FGS 系统主要在近红外(NIR,700-900 nm)波长下运行,
组织发色团吸光度、自发荧光和散射降至局部最小值,从而实现高对比度
成像深度可达厘米。许多靶向近红外造影剂正在开发中,包括
神经和前列腺特异性探针共同将为前列腺切除术提供集成的 FGS 工具。在
美国超过 80% 的前列腺切除术是使用机器人辅助进行的,其中达芬奇手术机器人(直观
手术)是最常见的,并且标准配备了 NIR 荧光成像通道,能够
实时可视化。在此,我们将与博士合作。乔纳森·索格(Jonathan Sorger)(直觉外科)和斯科特·戴维斯
(达特茅斯)开发用于前列腺切除术的多色 FGS 解决方案,可突出显示癌症和神经组织
以改善患者的治疗效果。前列腺特异性膜抗原 (PSMA) 在大多数细胞中过度表达
前列腺癌使其成为前列腺癌成像的有希望的目标。一些分子已经表明
标记后对 PSMA 具有高亲和力,这已被广泛研究,其中 800 nm PSMA tar-
IS-002已成功完成由Intuitive Surgical赞助的I期临床试验。在此,我们将
开发一种 NIR、光谱不同、神经特异性荧光团,与 PSMA 靶向 IS-002 共同给药,以
将这种新的 FGS 范例带给前列腺癌患者。在令人兴奋的初步工作中,我们的团队合成了
可使用临床 FGS 系统成像的 NIR 神经特异性荧光团。在此,700 nm NIR 神经特异性
cific 探针将进行综合调整,以便与 PSMA 特异性 800 nm IS-002 共同给药,并进行验证
未来将转化为引导前列腺切除术。这些目标将通过以下具体目标来实现:
目标 1:合成 700 nm NIR 神经特异性 FGS 探针。目标 2:量化临床前药理学和毒理学
NIR 神经特异性探针与 IS-002 共同施用的生态学。目标 3:选择先导神经特异性探针
通过神经癌和前列腺癌特异性对比展示与 IS-002 联合给药。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Summer Lynne Gibbs其他文献
Summer Lynne Gibbs的其他文献
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{{ truncateString('Summer Lynne Gibbs', 18)}}的其他基金
Administrative Supplement - First-in-human clinical translation of a near-infrared, nerve-specific fluorophore to facilitate tissue-specific fluorescence-guided surgery
行政补充-近红外神经特异性荧光团的首次人体临床转化,以促进组织特异性荧光引导手术
- 批准号:
10862946 - 财政年份:2023
- 资助金额:
$ 61.13万 - 项目类别:
A Novel Fluorescence Imaging Platform to Predict Response to Combinatorial Tyrosine Kinase Inhibitors
预测组合酪氨酸激酶抑制剂反应的新型荧光成像平台
- 批准号:
10356738 - 财政年份:2022
- 资助金额:
$ 61.13万 - 项目类别:
Fluorescence Guided Surgery using Near Infrared Nerve-specific Probes for Cranial Nerve Preservation
使用近红外神经特异性探针进行荧光引导手术以保留脑神经
- 批准号:
10608732 - 财政年份:2022
- 资助金额:
$ 61.13万 - 项目类别:
Nerve-Specific Fluorophores for Improved Nerve Sparing during Prostatectomy using the Clinical Fluorescence Guided Surgery Infrastructure
使用临床荧光引导手术基础设施,神经特异性荧光团可改善前列腺切除术期间的神经保护
- 批准号:
10311445 - 财政年份:2021
- 资助金额:
$ 61.13万 - 项目类别:
Nerve-specific Fluorophores for Improved Nerve Sparing during Prostatectomy using the Clinical Fluorescence Guided Surgery Infrastructure
使用临床荧光引导手术基础设施,神经特异性荧光团可改善前列腺切除术期间的神经保护
- 批准号:
10540590 - 财政年份:2021
- 资助金额:
$ 61.13万 - 项目类别:
Mechanistic understanding of the lifecycle of a circulating hybrid cell
对循环混合细胞生命周期的机制理解
- 批准号:
10316094 - 财政年份:2021
- 资助金额:
$ 61.13万 - 项目类别:
Nerve-Specific Fluorophores for Improved Nerve Sparing during Prostatectomy using the Clinical Fluorescence Guided Surgery Infrastructure
使用临床荧光引导手术基础设施,神经特异性荧光团可改善前列腺切除术期间的神经保护
- 批准号:
10461857 - 财政年份:2021
- 资助金额:
$ 61.13万 - 项目类别:
Mechanistic understanding of the lifecycle of a circulating hybrid cell
对循环混合细胞生命周期的机制理解
- 批准号:
10629382 - 财政年份:2021
- 资助金额:
$ 61.13万 - 项目类别:
Nerve-Specific Fluorophores for Improved Nerve Sparing during Prostatectomy using the Clinical Fluorescence Guided Surgery Infrastructure
使用临床荧光引导手术基础设施,神经特异性荧光团可改善前列腺切除术期间的神经保护
- 批准号:
10614614 - 财政年份:2021
- 资助金额:
$ 61.13万 - 项目类别:
Mechanistic understanding of the lifecycle of a circulating hybrid cell
对循环混合细胞生命周期的机制理解
- 批准号:
10412136 - 财政年份:2021
- 资助金额:
$ 61.13万 - 项目类别:
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