Targeted radiotherapy of brain tumours

Zalutsky, Michael R.

doi:10.1038/sj.bjc.6601771

Cited by 43 publications

(23 citation statements)

References 25 publications

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“…[8][9][10] As Nimotuzumab is an IGg1 humanized mAb, it could activate more efficiently immune effector cells in the tumor area than murine mAbs. 42 The visual inspection of the processed scintigraphic images and the biodistribution calculations revealed that 188 Re-Nimotuzumab was retained in tumour cavity and adjacent malignant tissues for a long period.…”

Section: Discussionmentioning

confidence: 99%

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Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

Casacó

López²,

García³

et al. 2008

Cancer Biology & Therapy

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This manuscript has been published online, prior to printing.Once the issue is complete and page numbers have been assigned, the citation will change accordingly.Radioimmunotherapy (RIT) may improve the management of malignant gliomas. A Phase I clinical trial was performed to evaluate, for the first time, the toxicity and clinical effect of an intracavitary administration of a single dose of Nimotuzumab (h-R3) labeled wit 188 Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Three patients with anaplastic astrocytoma (AA) and 8 with glioblastoma multiforme (GBM) were intended to be treated with 3 mg of mAb labelled with 10 or 15 mCi of 188 Re. In patients treated with 10 mCi (n = 6) transitory worsening of pre-existing neurological symptoms were observed. Two patients treated with 15 mCi (n = 4) developed early severe neurological symptoms and one also developed late severe toxicity (radionecrosis). In the group treated with 10 mCi, 1 GBM patient died in progression 6 months after the treatment, 2 patients (1 GBM and 1 AA) developed stable disease during 3 months. One GBM patient had partial response for more than 1 year and 2 patients (1 GBM and 1 AA) were asymptomatic and in complete response after 3 years of treatment. Maximal tolerated dose of the radioimmunoconjugate 188 Re-Nimotuzumab was 3 mg of the h-R3 labelled with 10 mCi of 188 Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas.

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Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9][10] The infusion of radiolabelled monoclonal antibodies directly into the postsurgical resection cavity has enabled the delivery of high radiation doses to the affected area without important harm to the surrounding normal brain tissue or distant organs.…”

Section: Introductionmentioning

confidence: 99%

Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

Casacó

López²,

García³

et al. 2008

Cancer Biology & Therapy

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“…Due to this high linear energy transfer (LET), a-emitters induce cell death with only few nuclear hits to the target cell. There have been numerous pre-clinical studies conducted using RIT involving a-emitters, but so far only clinical studies involving acute myeloid leukemia and glioblastoma patients have been reported [20].…”

Section: Replacing 2 Gy Tbi With Rit In a Non-myeloablative Regimen Fmentioning

confidence: 99%

Radioimmunotherapy as non-myeloablative conditioning for allogeneic marrow transplantation

Bethge¹,

Wilbur²,

Sandmaier³

2006

Leukemia & Lymphoma

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Radioimmunotherapy (RIT) combines the advantages of specific immunotherapy with the cytotoxicity of radionuclides resulting in targeted radiation therapy. In the setting of allogeneic hematopoietic cell transplantation (HCT), RIT can be used to both target tumor cells and to suppress immunocompetent recipient cells. RIT with beta-emitters has been successfully used for further dose intensification of myeloablative conditioning regimens for HCT. Alpha-emitters with their short path length and high linear energy transfer bear certain advantages over beta-emitters if used to target hematopoietic cells. Using a canine model of non-myeloablative HCT, one could demonstrate that pre-transplant RIT with the alpha-emitter bismuth-213 (213Bi) coupled to anti-CD45 or anti-TCRalphabeta monoclonal antibodies (mAb) together with post-grafting immunosuppression with mycophenolate mofetil and cyclosporine can achieve stable engraftment and long-term mixed chimerism. The two mAbs may allow a tailored approach to RIT in non-myeloablative conditioning with 213Bi-anti-CD45 used for patients with hematologic malignancies and 213Bi-anti-TCRalphabeta for non-malignant diseases. Extensive studies of biodistribution, dose de-escalation and toxicity provide the basis for the conception of clinical trials using RIT for non-myeloablative HCT.

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“…It is beyond the scope of this review to discuss all published studies. For a detailed review on RIT, see Zalutsky, 111 Carlsson et al, 110 Seidl 114 and Dietrich 115 . Table 1 summarizes the studies reviewed here.…”

Section: Particle Therapymentioning

confidence: 99%

“…By contrast, 131 I is a medium-energy b (range 0.9 mm) and g radiation emitter that significantly contributes to the whole-brain radiation dose. 110 Clinical experience with radioimmunotherapy The majority of RIT studies in gliomas are performed with antitenascin-C or antiEGFR mAb. The expression of tenascin and of EGFR increases with advancing brain tumour grade with .90% of GBM biopsies exhibiting tenascin overexpression, 111 while EGFR overexpression varies between 31% and 95% in patients with GBM.…”

Section: Particle Therapymentioning

confidence: 99%

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

Neubeck¹,

Seidlitz²,

Kitzler³

et al. 2015

BJR

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Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses .60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets.

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Targeted radiotherapy of brain tumours

Cited by 43 publications

References 25 publications

Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

Phase I single-dose study of intracavitary-administered Nimotuzumab labeled with 188-Re in adult recurrent high-grade glioma

Radioimmunotherapy as non-myeloablative conditioning for allogeneic marrow transplantation

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

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