scholarly journals Beyond the Barrier: Targeted Radionuclide Therapy in Brain Tumors and Metastases

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 376 ◽  
Author(s):  
Puttemans ◽  
Lahoutte ◽  
D’Huyvetter ◽  
Devoogdt
Keyword(s):  
Brain Tumors ◽  
Radionuclide Therapy ◽  
Clinical Investigation ◽  
Metastatic Cancer ◽  
Targeted Radionuclide Therapy ◽  
Newly Diagnosed ◽  
Cytotoxic Potential ◽  
Therapeutic Modalities ◽  
Systemic Treatments ◽  
The Brain

Brain tumors are notoriously difficult to treat. The blood-brain barrier provides a sanctuary site where residual and metastatic cancer cells can evade most therapeutic modalities. The delicate nature of the brain further complicates the decision of eliminating as much tumorous tissue as possible while protecting healthy tissue. Despite recent advances in immunotherapy, radiotherapy and systemic treatments, prognosis of newly diagnosed patients remains dismal, and recurrence is still a universal problem. Several strategies are now under preclinical and clinical investigation to optimize delivery and maximize the cytotoxic potential of pharmaceuticals with regards to brain tumors. This review provides an overview of targeted radionuclide therapy approaches for the treatment of primary brain tumors and brain metastases, with an emphasis on biological targeting moieties that specifically target key biomarkers involved in cancer development.

scholarly journals To the clinic of cancer metastasis to the brain

2021 ◽  
Vol 43 (2) ◽  
pp. 11-12
Author(s):  
Sh. I. Zheleznova ◽  
N. G. Cherkasova
Keyword(s):  
Brain Tumors ◽  
Brain Cancer ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Cancer Metastases ◽  
The Brain

While primary brain cancer is extremely rare, metastatic cancer is much more common. According to Thomson, almost half of all brain tumors are metastatic cancer (81 out of 181), according to Cushing, cancer metastases in the brain are 7.2%, according to Walsh - 6.4-7.7%, according to Crasting - 36.8%.

scholarly journals Preclinical Targeted α- and β−-Radionuclide Therapy in HER2-Positive Brain Metastasis Using Camelid Single-Domain Antibodies

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1017 ◽  
Author(s):  
Janik Puttemans ◽  
Yana Dekempeneer ◽  
Jos L. Eersels ◽  
Heleen Hanssens ◽  
Pieterjan Debie ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Metastatic Cancer ◽  
Brain Lesions ◽  
Single Domain ◽  
Histopathological Analysis ◽  
Breast Cancer Patients ◽  
Tumor Models ◽  
Single Domain Antibody ◽  
Her2 Positive ◽  
The Brain

HER2-targeted therapies have drastically improved the outcome for breast cancer patients. However, when metastasis to the brain is involved, current strategies fail to hold up to the same promise. Camelid single-domain antibody-fragments (sdAbs) have been demonstrated to possess favorable properties for detecting and treating cancerous lesions in vivo using different radiolabeling methods. Here we evaluate the anti-HER2 sdAb 2Rs15d, coupled to diagnostic γ- and therapeutic α- and β−-emitting radionuclides for the detection and treatment of HER2pos brain lesions in a preclinical setting. 2Rs15d was radiolabeled with 111In, 225Ac and 131I using DTPA- and DOTA-based bifunctional chelators and Sn-precursor of SGMIB respectively and evaluated in orthotopic tumor-bearing athymic nude mice. Therapeutic efficacy as well as systemic toxicity were determined for 131I- and 225Ac-labeled sdAbs and compared to anti-HER2 monoclonal antibody (mAb) trastuzumab in two different HER2pos tumor models. Radiolabeled 2Rs15d showed high and specific tumor uptake in both HER2pos SK-OV-3-Luc-IP1 and HER2pos MDA-MB-231Br brain lesions, whereas radiolabeled trastuzumab was unable to accumulate in intracranial SK-OV-3-Luc-IP1 tumors. Administration of [131I]-2Rs15d and [225Ac]-2Rs15d alone and in combination with trastuzumab showed a significant increase in median survival in 2 tumor models that remained largely unresponsive to trastuzumab treatment alone. Histopathological analysis revealed no significant early toxicity. Radiolabeled sdAbs prove to be promising vehicles for molecular imaging and targeted radionuclide therapy of metastatic lesions in the brain. These data demonstrate the potential of radiolabeled sdAbs as a valuable add-on treatment option for patients with difficult-to-treat HER2pos metastatic cancer.

Brain Tumor Detection via Asymmetry Quantification across Mid Sagittal Plane

2020 ◽  
Vol 13 ◽  
Author(s):  
Shoaib Amin Banday ◽  
Mohammad Khalid Pandit
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Sagittal Plane ◽  
Early Stage ◽  
Imaging Techniques ◽  
Complex Structure ◽  
Magnetic Resonance Images ◽  
Absolute Difference ◽  
Brain Hemispheres ◽  
The Brain

Introduction: Brain tumor is among the major causes of morbidity and mortality rates worldwide. According to National Brain Tumor Foundation (NBTS), the death rate has nearly increased by as much as 300% over last couple of decades. Tumors can be categorized as benign (non-cancerous) and malignant (cancerous). The type of the brain tumor significantly depends on various factors like the site of its occurrence, its shape, the age of the subject etc. On the other hand, Computer Aided Detection (CAD) has been improving significantly in recent times. The concept, design and implementation of these systems ascend from fairly simple ones to computationally intense ones. For efficient and effective diagnosis and treatment plans in brain tumor studies, it is imperative that an abnormality is detected at an early stage as it provides a little more time for medical professionals to respond. The early detection of diseases has predominantly been possible because of medical imaging techniques developed from past many decades like CT, MRI, PET, SPECT, FMRI etc. The detection of brain tumors however, has always been a challenging task because of the complex structure of the brain, diverse tumor sizes and locations in the brain. Method: This paper proposes an algorithm that can detect the brain tumors in the presence of the Radio-Frequency (RF) inhomoginiety. The algorithm utilizes the Mid Sagittal Plane as a landmark point across which the asymmetry between the two brain hemispheres is estimated using various intensity and texture based parameters. Result: The results show the efficacy of the proposed method for the detection of the brain tumors with an acceptable detection rate. Conclusion: In this paper, we have calculated three textural features from the two hemispheres of the brain viz: Contrast (CON), Entropy (ENT) and Homogeneity (HOM) and three parameters viz: Root Mean Square Error (RMSE), Correlation Co-efficient (CC), and Integral of Absolute Difference (IAD) from the intensity distribution profiles of the two brain hemispheres to predict any presence of the pathology. First a Mid Sagittal Plane (MSP) is obtained on the Magnetic Resonance Images that virtually divides brain into two bilaterally symmetric hemispheres. The block wise texture asymmetry is estimated for these hemispheres using the above 6 parameters.

scholarly journals Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumors ◽  
Ad Hoc ◽  
Superparamagnetic Iron Oxide ◽  
Conventional Radiotherapy ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

Organs dosimetry in targeted radionuclide therapy

2021 ◽  
pp. 109668
Author(s):  
Meshari Alnaaimi ◽  
Abdelmoneim Sulieman ◽  
Mohammed Alkhorayef ◽  
Hasan Salah ◽  
Musa Alduaij ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Targeted Radionuclide Therapy

scholarly journals Laser interstitial thermotherapy (LITT) for the treatment of tumors of the brain and spine: a brief review

2021 ◽  
Vol 151 (3) ◽  
pp. 429-442
Author(s):  
Clark Chen ◽  
Ian Lee ◽  
Claudio Tatsui ◽  
Theresa Elder ◽  
Andrew E. Sloan
Keyword(s):  
Brain Tumors ◽  
Minimally Invasive ◽  
Radiation Necrosis ◽  
Spinal Metastasis ◽  
Clinical Approach ◽  
Invasive Treatment ◽  
Primary Indication ◽  
Interstitial Thermotherapy ◽  
The Brain

Abstract Introduction Laser Interstitial Thermotherapy (LITT; also known as Stereotactic Laser Ablation or SLA), is a minimally invasive treatment modality that has recently gained prominence in the treatment of malignant primary and metastatic brain tumors and radiation necrosis and studies for treatment of spinal metastasis has recently been reported. Methods Here we provide a brief literature review of the various contemporary uses for LITT and their reported outcomes. Results Historically, the primary indication for LITT has been for the treatment of recurrent glioblastoma (GBM). However, indications have continued to expand and now include gliomas of different grades, brain metastasis (BM), radiation necrosis (RN), other types of brain tumors as well as spine metastasis. LITT is emerging as a safe, reliable, minimally invasive clinical approach, particularly for deep seated, focal malignant brain tumors and radiation necrosis. The role of LITT for treatment of other types of tumors of the brain and for spine tumors appears to be evolving at a small number of centers. While the technology appears to be safe and increasingly utilized, there have been few prospective clinical trials and most published studies combine different pathologies in the same report. Conclusion Well-designed prospective trials will be required to firmly establish the role of LITT in the treatment of lesions of the brain and spine.

scholarly journals Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

2021 ◽  
Vol 14 (7) ◽  
pp. 626
Author(s):  
Julie Bolcaen ◽  
Shankari Nair ◽  
Cathryn H. S. Driver ◽  
Tebatso M. G. Boshomane ◽  
Thomas Ebenhan ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Radionuclide Therapy ◽  
Kinase Inhibitors ◽  
Nuclear Imaging ◽  
Therapy Resistance ◽  
Targeted Radionuclide Therapy ◽  
Therapy Strategy ◽  
Dismal Prognosis

Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

scholarly journals MET-05 Clinical investigation of treatment results and recurrence patterns of metastatic brain tumors from the viewpoint of postoperative irradiation

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii19-ii19
Author(s):  
Tetsuo Hashiba ◽  
Haruka Kawano ◽  
Katsuya Ueno ◽  
Qiang Lee ◽  
Haruna Isozaki ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Tumors ◽  
Clinical Investigation ◽  
Postoperative Radiotherapy ◽  
En Bloc Resection ◽  
Metastatic Brain Tumors ◽  
Treatment Results ◽  
En Bloc ◽  
Postoperative Radiation Therapy ◽  
Observation Period

Abstract While whole brain radiation therapy (WBRT) had been the standard postoperative radiation therapy for metastatic brain tumors for long time, recently local radiation therapy (LRT) has be become to be a new standard due to the accumulation of clinical evidences. Treatment results and pattern of recurrence were retrospectively analyzed from view point of postoperative radiotherapy. In this study, totally 69 patients were included and they were divided into WBRT group or LRT group. We analyzed the number of lesions, treated era, overall survival after diagnosis of metastasis (OS), recurrence free survival after RT (RFS), and patterns of recurrences. The subjects consisted of 37males and 32 females and average age was 61.7 years old. There were 49 cases in the WBRT group and 20 cases in the LRT group. While all cases before November 2017 had WBRT performed, LRT was adopted mainly in cases with a small number of metastases since December 2017. Although there was a difference in the observation period between the two groups, OS tended to be longer in the LRT group (P=0.08), while RFS tended to be shorter in the LRT group (P=0.08). Radiological recurrence after RT was observed in 7 cases in both groups, and in WBRT group, all cases were local recurrence, whereas in LRT group, all cases were new lesions or disseminated recurrence. Although there are biases such as the difference in observation period between the two groups and the tendency to adopt WBRT in cases with a large number of metastases, there is a possibility that postoperative LRT is not inferior to WBRT, especially for cases with a small number of metastases. However, we have experienced some cases of disseminated recurrence, and so it is necessary to consider the resection fashion such as whether en-bloc resection or piece meal resection when selecting postoperative RT.

scholarly journals Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 599
Author(s):  
Stephen Ahenkorah ◽  
Irwin Cassells ◽  
Christophe M. Deroose ◽  
Thomas Cardinaels ◽  
Andrew R. Burgoyne ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Radionuclide Therapy ◽  
Chemical Properties ◽  
High Energy ◽  
Magic Bullet ◽  
Targeted Radionuclide Therapy ◽  
Energy Photon ◽  
Normal Tissues ◽  
Preclinical And Clinical Studies ◽  
Alpha Therapy

In contrast to external high energy photon or proton therapy, targeted radionuclide therapy (TRNT) is a systemic cancer treatment allowing targeted irradiation of a primary tumor and all its metastases, resulting in less collateral damage to normal tissues. The α-emitting radionuclide bismuth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

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