[68Ga] Ga-PSMA-11 PET/MR-imaging of Malignant Intra-axial Brain Tumors; Primary Assessment of PSMA Expression, Optimization of Compound Delivery and Determination of Theranostic Potential
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- SUV tumor-to-background ratio
研究概览
简要总结
PSMA is a transmembrane protein specifically expressed in the vascular endothelium of malignant brain tumors, most notably glioblastoma and not in healthy brain parenchyma. It has been shown to be involved in (neo)angiogenesis and endothelial cell invasion. By means of 68Ga-labeled PSMA ligands, investigators are able to non-invasively visualize/quantify PSMA expression in glioblastoma (neo)vasculature in vivo by means of PET.
The primary aim of this study is to confirm PSMA as suitable diagnostic and potential theranostic target in patients with intra-axial brain tumors by means of [68Ga]Ga-PSMA-HBEC-CC ([68Ga]Ga-PSMA-11) PET.
The secondary aim is to assess whether uptake is increased with intra-arterial injection in those tumors that show uptake after intravenous injection of [68Ga]Ga-PSMA-11.
详细描述
Brain tumors have a major impact due to both high morbidity and mortality. Primary brain tumors (glioma) have a low incidence (5-7:100,000), but the highest loss of life years compared to other cancer types. Glioblastoma without mutations in the Isocitrate Dehydrogenase gene (IDHwt), are the most frequent and the most aggressive of all primary malignant brain tumors. They account for 48% of all the primary malignant brain tumors and 15% of all primary brain tumors. Treatment consists of resection, radiotherapy and systemic chemotherapy. Nevertheless the current prognosis is still poor with a 1-, 2- and 5-year survival of respectively 40%, 17% and 6%.
Secondary brain tumors (brain metastases) are frequent, occurring in 15% of cancer patients (incidence 50-70:100,000). The prevalence of brain metastases is rising due to better extracranial local cancer control with systemic treatment resulting in more surviving patients with good local tumor control, but with brain metastases.
A recently discovered potential target for (localized) therapy of glioblastoma is PSMA. PSMA was originally found to be specifically expressed in normal prostate, and overexpressed in almost all stages of prostate cancer. In recent years, PSMA was also found to be expressed in tumor-associated (neo)vasculature in many other solid tumors, including glioblastoma.
PSMA is distinct from other vascular targets, such as vascular endothelial growth factor, endoglin, or the integrins involved in the general process of angiogenesis, as these latter are not specific to tumor vasculature. PSMA, in contrast, is not expressed in normal vasculature and is only minimally expressed in a subset of normal glial cells. PSMA therewith represents the most specific (neo)vascular target for glioblastoma currently known.
This specificity makes PSMA an ideal target for delivery of a cytotoxic agent or a radionuclide designed to tumor vasculature destruction. Particularly in intra-axial brain tumors such as glioblastoma, therapeutic targeting of (neo)vasculature is attractive as it may be exposed to a therapeutic agent much more readily than the tumor parenchyma itself, which is protected by the blood-brain barrier.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Radiologically presumed/histologically confirmed.
- •glioma (grade II-IV) showing enhancement on post-contrast MRI
- •brain metastases
- •Planned for (re-)resection
- •Age > 18 years old
- •Good clinical condition (Karnofsky performance status score >70)
- •Ability and willingness to provide written informed consent
排除标准
- •Impaired renal function: eGFR (MDRD) <30 ml/min/1,73 m2
- •Impaired liver function :AST and ALT > 2.5 8 ULN
- •Karnofsky Performance score of less than 70
- •Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 3 years prior to enrollment, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
- •Known history of cerebrovascular disease (e.g. ischemic stroke, cerebral hemorrhage)
- •Severe claustrophobia prohibiting PET/MRI scanning
- •A neurologic or psychiatric condition impairing judgement, making adequate informed consent impossible
- •Any psychological, familial, sociological or geographical condition hampering participation
- •Contra-indications for PET imaging
- •Pregnancy or lactation
- •Known allergic reaction to therapeutic radiopharmaceuticals
- •Contra-indications for MR imaging:
- •Metal implants or fragments of the type which may concentrate radiofrequency fields or cause tissue damage from twisting in a magnetic field:
- •metal plates, wires, screws or rods
- •surgical (brain) clips or staples
- •metallic fragments in or near eyes or blood vessels
- •metallic cardiac valve(s)
- •a cardiac implantable electronic device (pacemaker, wires, implantable cardioverter-defibrillator (ICD))
- •eye implants
- •ear or cochlear implants
- •a drug pump implant
- •a nerve stimulator
- •dental fillings and bridges
- •artificial joints
- •penile implants
- •tubal ligation clips
- •non-removable piercing
- •tattoos containing metal traces
- •Known allergic reaction to gadolinium-based contrast agents
- •Contra-indications for arterial catheterization:
- •Known local infection thrombus or distorted anatomy at the puncture site
- •Known severe peripheral vascular disease or femoral artery disease, which makes the femoral approach impossible
- •Known severe coagulopathy (spontaneous prolonged PT with an INR > 2.5)
- •In case of the use of anticoagulation: an absolute contra-indication to temporarily stop or bridge the anti-coagulation.
- •Known severe thrombocytopenia (platelet count 50 x 109/L)
- •Allergic reaction to iodine containing contrast agent
- •A physical, neurologic or psychological condition preventing the patient to lay still for the duration of the procedure (± 2h)
结局指标
主要结局
SUV tumor-to-background ratio
时间窗: 1 week
SUV tumor-to-background ratio
tumor SUV (upon intravenous and intra-arterial injection),
时间窗: 1 day
tumor SUV (upon intravenous and intra-arterial injection
Biodistribution
时间窗: 1 week
Biodistribution
correlation between SUV and the degree of immunohistochemical PSMA staining
时间窗: 1 week
correlation between SUV and the degree of immunohistochemical PSMA staining
次要结局
未报告次要终点
研究者
Dr. S.E.M. Veldhuijzen van Zanten
Scientific investigator
Erasmus Medical Center