RESUMO
We describe for the first time the synthesis of biocompatible TiO2 nanoparticles containing a functional NH2 group which are easily dispersible in water. The synthesis of water dispersible TiO2 nanoparticles coated with mercaptosuccinic acid is also reported. We show that it is possible to exchange the stearic acid from pre-synthesised fatty acid-coated anatase 5-nm nanoparticles with a range of organic ligands with no change in the size or morphology. With further organic functionalisation, these nanoparticles could be used for medical imaging or to carry cytotoxic radionuclides for radioimmunotherapy where ultrasmall nanoparticles will be essential for rapid renal clearance.
RESUMO
INTRODUCTION: Changes in 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) incorporation by tumors, detected using positron emission tomography, during response to chemotherapy are utilized clinically in patient management. Here, the effect of treatment with growth-inhibitory doses of the anti-human epidermal growth factor receptor-2 antibody trastuzumab (Herceptin) on the incorporation of FDG by breast tumor cells was measured along with hexokinase (HK) and glucose transport to determine the potential of FDG-positron emission tomography in predicting response to these biological anti-cancer therapies and their modulatory effects on the steps involved in FDG incorporation. METHODS: The sensitivity to trastuzumab of three breast tumor cell lines, SKBr3, MDA-MB-453 and MDA-MB-468, expressing human epidermal growth factor receptor-2 at high, medium and low levels, respectively, was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay over a 6-day period, and a clonogenic assay was carried out after 7- and 10-day exposures. FDG incorporation by cells treated with growth-inhibitory doses of trastuzumab was carried out after 4 h and 2, 4 and 6 days of treatment. Glucose transport (rate of uptake of the non-metabolizable analogue [(3)H]O-methyl-D-glucose), HK activity and lactate production were measured on cells treated with inhibitory doses of trastuzumab for 6 days. RESULTS: The IC(50) doses for SKBr3 and MDA-MB-453 and the IC(20) dose for MDA-MB-468 after 6 days of treatment with trastuzumab were 0.25, 1 and 170 µg/ml, respectively. FDG incorporation by SKBr3 and MDA-MB-453 cells was found to be decreased using IC(50) doses of trastuzumab for 6 days. At the IC(50) doses, FDG incorporation was also decreased at 4 days and, in the case of MDA-MB-453, even after 4 h of treatment. Decreased FDG incorporation corresponded with decreased HK activity in these cells. Lactate production, previously suggested to be a potential measure of response, was found to be significantly decreased by SKBr3 and MDA-MB-453 cells responding to trastuzumab. CONCLUSION: FDG incorporation at the tumor cell level is modulated by treatment with growth-inhibitory doses of trastuzumab due to modulation of HK activity. Changes in lactate production may also be a useful determinant of response to trastuzumab.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Neoplasias da Mama/patologia , Fluordesoxiglucose F18/metabolismo , Hexoquinase/metabolismo , Ácido Láctico/biossíntese , Receptor ErbB-2/imunologia , Anticorpos Monoclonais Humanizados , Transporte Biológico/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Glucose/metabolismo , Humanos , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismo , Trastuzumab , Ensaio Tumoral de Célula-TroncoRESUMO
The biotin-avidin affinity system is exploited in pre-targeted imaging using avidin-conjugated antibodies. (18)F-FDG is available at all PET centres. (18)F-FDG forms oximes by reaction with oxyamine. Herein we describe the synthesis of oxyamine-funtionalised biotin, its (18)F-labelling by conjugation with (18)F-FDG and confirm its ability to interact with avidin.