[show abstract][hide abstract] ABSTRACT: A novel approach using nano-technology enhanced radiation modalities is investigated. The proposed methodology uses antibodies labeled with organically inert metals with a high atomic number. Irradiation using photons with energies in the kilo-electron volt (keV) range shows an increase in dose due to a combination of an increase in photo-electric interactions and a pronounced generation of Auger and/or Coster-Krönig (A-CK) electrons. The dependence of the dose deposition on various factors is investigated using Monte Carlo simulation models. The factors investigated include agent concentration, spectral dependence looking at mono-energetic sources as well as classical bremsstrahlung sources. The optimization of the energy spectrum is performed in terms of physical dose enhancement as well as the dose deposited by Auger and/or Coster-Krönig electrons and their biological effectiveness. A quasi-linear dependence on concentration and an exponential decrease within the target medium is observed. The maximal dose enhancement is dependent on the position of the target in the beam. Apart from irradiation with low-photon energies (10-20 keV) there is no added benefit from the increase in generation of Auger electrons. Interestingly, a regular 110 kVp bremsstrahlung spectrum shows a comparable enhancement in comparison with the optimized mono-energetic sources. In conclusion we find that the use of enhanced nano-particles shows promise to be implemented quite easily in regular clinics on a physical level due to the advantageous properties in classical beams.
Physics in Medicine and Biology 08/2010; 55(16):4509-20. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Melanocortin-1 receptor (MC1-R) and melanin are two attractive melanoma-specific targets for peptide-targeted radionuclide therapy for melanoma. Radiolabeled peptides targeting MC1-R/melanin can selectively and specifically target cytotoxic radiation generated from therapeutic radionuclides to melanoma cells for cell killing, while sparing the normal tissues and organs. This review highlights the recent advances of peptide-targeted radionuclide therapy of melanoma targeting MC1-R and melanin. The promising therapeutic efficacies of 188Re-(Arg(11))CCMSH (188Re-[Cys(3,4,10), D-Phe(7),Arg(11)]-alpha-MSH(3-13)), 177Lu- and 212Pb-labeled DOTA-Re(Arg(11))CCMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[ReO-(Cys(3,4,10), D-Phe(7), Arg(11))]-alpha-MSH(3-13)) and 188Re-HYNIC-4B4 (188Re-hydrazinonicotinamide-Tyr-Glu-Arg-Lys-Phe-Trp-His-Gly-Arg-His) in preclinical melanoma-bearing models demonstrate an optimistic outlook for peptide-targeted radionuclide therapy for melanoma. Peptide-targeted radionuclide therapy for melanoma will likely contribute in an adjuvant setting, once the primary tumor has been surgically removed, to treat metastatic deposits and for treatment of end-stage disease. The lack of effective treatments for metastatic melanoma and end-stage disease underscores the necessity to develop and implement new treatment strategies, such as peptide-targeted radionuclide therapy.
Critical Reviews in Oncology/Hematology 05/2008; 67(3):213-28. · 4.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: ObjectivesTo evaluate the initial response and outcomes (quality of life and presence of side effects) in patients with advanced neuroendocrine
tumours (NET) after treatment with radiolabelled somatostatin analogues: 90Y-DOTAT-yr3-octreotide (90Y-DOTATOC) and 177Lu-DOTA-Tyr3- octreotate (177Lu-DOTATATE).
Material and methodsThe study included 5 patients with advanced NET referred to European centres for treatment with 90Y-DOTATOC and 177Lu-DOTATATE after lack of response to conventional treatment. The mean age was 45.6 years (29-68 years). Response to therapy
was assessed according to: (1) RECIST criteria, as complete response, partial response, stable disease or disease progression,
(2) post-treatment survival time and (3) quality of life, using the Karnofsky performance index.
ResultsAll patients survived for >20 months after treatment; mean survival time was 28 months. At the time of writing, three of the
patients are alive after 20, 26 and 37 months. Partial response was observed in one patient, stable disease in three and disease
progression in the fifth patient. A good-to-excellent post-treatment quality of life was observed in all patients.
ConclusionTherapy with radiolabelled somatostatin analogues showed promising results in patients with advanced NET, with a partial response
or disease stabilisation in four of the five patients, who have enjoyed an extended survival period and an improved quality
Clinical and Translational Oncology 12/2008; 11(1):48-53. · 1.28 Impact Factor
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