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1.
ESMO Open ; 7(1): 100365, 2022 02.
Article in English | MEDLINE | ID: mdl-34998092

ABSTRACT

BACKGROUND: We assessed the capacity of epidermal growth factor receptor (EGFR)-targeted immunoliposomes to deliver cargo to brain tumor tissue in patients with relapsed glioblastoma harboring an EGFR amplification. We aimed to assess the tolerability and effectiveness of anti-EGFR immunoliposomes loaded with doxorubicin (anti-EGFR ILs-dox) in glioblastoma multiforme patients. PATIENTS AND METHODS: Patients with EGFR-amplified, relapsed glioblastoma were included in this phase I pharmacokinetic trial. Patients received up to four cycles of anti-EGFR ILs-dox. Twenty-four hours later, plasma and cerebrospinal fluid (CSF) samples were obtained. In addition, we also treated three patients with anti-EGFR ILs-dox before resection of their relapsed glioblastoma. Doxorubicin concentrations were measured in plasma, CSF, and tumor tissue. Safety and efficacy parameters were also obtained. RESULTS: There were no or negligible levels of doxorubicin found in the CSF demonstrating that anti-EGFR ILs-dox are not able to cross the blood-brain barrier (BBB). However, significant levels were detected in glioblastoma tissue 24 h after the application, indicating that the disruption of BBB integrity present in high-grade gliomas might enable liposome delivery into tumor tissue. No new safety issues were observed. The median progression-free survival was 1.5 months and the median overall survival was 8 months. One patient undergoing surgery had a very long remission suggesting that neoadjuvant administration may have a positive effect on outcome. CONCLUSIONS: We clearly demonstrate that anti-EGFR-immunoliposomes can be targeted to EGFR-amplified glioblastoma and cargo-in this case doxorubicin-can be delivered, although these immunoliposomes do not cross the intact BBB. (The GBM-LIPO trial was registered as NCT03603379).


Subject(s)
Brain Neoplasms , Glioblastoma , Brain Neoplasms/drug therapy , Doxorubicin/pharmacokinetics , Doxorubicin/therapeutic use , ErbB Receptors , Glioblastoma/drug therapy , Humans , Liposomes
4.
Eur J Nucl Med Mol Imaging ; 37(7): 1335-44, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20157707

ABSTRACT

PURPOSE: Functionally critically located gliomas represent a challenging subgroup of intrinsic brain neoplasms. Standard therapeutic recommendations often cannot be applied, because radical treatment and preservation of neurological function are contrary goals. The successful targeting of gliomas with locally injected beta radiation-emitting (90)Y-DOTAGA-substance P has been shown previously. However, in critically located tumours, the mean tissue range of 5 mm of (90)Y may seriously damage adjacent brain areas. In contrast, the alpha radiation-emitting radionuclide (213)Bi with a mean tissue range of 81 microm may have a more favourable toxicity profile. Therefore, we evaluated locally injected (213)Bi-DOTA-substance P in patients with critically located gliomas as the primary therapeutic modality. METHODS: In a pilot study, we included five patients with critically located gliomas (WHO grades II-IV). After diagnosis by biopsy, (213)Bi-DOTA-substance P was locally injected, followed by serial SPECT/CT and MR imaging and blood sampling. Besides feasibility and toxicity, the functional outcome was evaluated. RESULTS: Targeted radiopeptide therapy using (213)Bi-DOTA-substance P was feasible and tolerated without additional neurological deficit. No local or systemic toxicity was observed. (213)Bi-DOTA-substance P showed high retention at the target site. MR imaging was suggestive of radiation-induced necrosis and demarcation of the tumours, which was validated by subsequent resection. CONCLUSION: This study provides proof of concept that targeted local radiotherapy using (213)Bi-DOTA-substance P is feasible and may represent an innovative and effective treatment for critically located gliomas. Primarily non-operable gliomas may become resectable with this treatment, thereby possibly improving the prognosis.


Subject(s)
Alpha Particles/therapeutic use , Glioma/radiotherapy , Heterocyclic Compounds, 1-Ring/therapeutic use , Organometallic Compounds/therapeutic use , Substance P/analogs & derivatives , Adult , Feasibility Studies , Glioma/metabolism , Heterocyclic Compounds, 1-Ring/administration & dosage , Heterocyclic Compounds, 1-Ring/adverse effects , Heterocyclic Compounds, 1-Ring/pharmacokinetics , Humans , Injections , Middle Aged , Organometallic Compounds/administration & dosage , Organometallic Compounds/adverse effects , Organometallic Compounds/pharmacokinetics , Pilot Projects , Substance P/administration & dosage , Substance P/adverse effects , Substance P/pharmacokinetics , Substance P/therapeutic use , Treatment Outcome
5.
Br J Neurosurg ; 22(5): 684-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18661318

ABSTRACT

A 71-year-old patient presented with low back pain and slowly progressive weakness of both legs. Within a few hours after lumbar myelography, paraplegia below level L2 evolved. MR-imaging revealed a discogenic stenosis at level Th10/11. Immediate decompression by costo-transversectomy led to reversal of the neurological deficits.


Subject(s)
Intervertebral Disc Displacement/surgery , Low Back Pain/etiology , Lumbar Vertebrae/surgery , Paraplegia/surgery , Thoracic Vertebrae/surgery , Acute Disease , Aged , Calcinosis/surgery , Decompression, Surgical/methods , Female , Humans , Intervertebral Disc Displacement/complications , Magnetic Resonance Imaging , Myelography/adverse effects , Paraplegia/etiology , Treatment Outcome
6.
Talanta ; 44(9): 1671-82, 1997 Sep.
Article in English | MEDLINE | ID: mdl-18966906

ABSTRACT

The emergence of the fiber-optic sensor era has stimulated investigations to create synthetic fluororeceptors capable of signaling the binding of metal ions. To fulfill this purpose, a new concept is presented: the metal-promoted shift of equilibrium between the two fluorescent forms of a synthetic receptor able to dimerize and to specifically recognize a metal ion by multiple non-covalent bonds. The thermodynamics of the dimerization itself and the dimer-zinc interactions are analyzed in terms of association constants. It is demonstrated that finely tuning the equilibrium between the monomeric and dimeric forms by controlling the pH, permits the alternate selective recognition and signaling of zinc or cadmium.

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