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Applications of radiolabelled monoclonal antibodies in the management of malignant disease of the central nervous system
Başlık:
Applications of radiolabelled monoclonal antibodies in the management of malignant disease of the central nervous system
Yazar:
Papanastassiou, Varnavas, author.
ISBN:
9780438082847
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (299 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
Radiolabelled monoclonal antibodies (mab) have been in use for some 15 years now in the management of malignant disease. More recently regional administration has tried to circumvene some of the main problems of systemic therapy that resulted in a poor therapeutic index. The central nervous system (CNS) and the intrathecal space provide an ideal situation for the development of this form of treatment. This thesis investigates some of the latest applications of radiolabelled mab technology in radioimmunodetection and radioimmunotherapy of CNS malignancy. A new method for labelling mabs with 99mTc was evaluated and shown to be successful for both IgG1 and IgG2a classes of antibodies. Furthermore these radiolabels were administered for the first time into a patient's CNS, both via the intrathecal route and into tumour resection cavities, without toxicity. Examples of some of the imaging studies undertaken are given. These highlight the potential of this type of conjugates both for radioimmunolocalisation in the CNS and for planning and assessing therapy. Two groups of patients were treated in the clinical setting using radioiodinated mabs; patients with leptomeningeal spread of primitive neuroectodermal tumours (PNET) and those with recurrent or cystic malignant gliomas. Five patients were treated in the first group, which was partly a continuation of work done by the Bristol Brain Tumour Group in conjunction with the ICRF Paediatric Oncology laboratory at the Institute of Child Health in London in previous years. This study has concentrated on a single disease entity, PNET, with special emphasis on formulating and developing pharmacokinetic and dosimetric models. In addition, some insight was gained into the effects and mechanics of repeated intrathecal therapy. The second group of patients was included in an essentially phase I/II study of intracavitary administration of radioimmunoconjugates into malignant cystic gliomas or resection cavities of recurrent tumours. Seven patients received nine treatments with acceptable toxicity. Once again, pharmacokinetics and dosimetry were studied in detail and models developed for this novel form of therapy. One patient received repeated therapy one month later and the differences in the pharmacokinetics of the two administrations are analysed.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(686848.1) | 686848-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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