RESUMEN
Whatman 3MM™ and Tec-Control™ systems were evaluated as ITLC-SG alternatives for 99mTc-radiopharmaceuticals. They compare well in accuracy and reproducibility, and are faster and more convenient than ITLC-SG. Tec-Control™ radiochemical purity values for 99mTc-sestamibi were more conservative than ITLC-SG. Full solvent migration was not reproduced for 99mTc-tetrofosmin in Tec-Control™, and for this Whatman 3MM™ is preferred. Developing times were 10-15 min, 7-9 min and ~1min for ITLC-SG, Whatman 3MM™ and Tec-Control™, respectively. Overall, Tec-Control™ strips are preferred due to speed and ease of use.
Asunto(s)
Cromatografía en Capa Delgada/métodos , Tecnecio/aislamiento & purificación , Antimonio/aislamiento & purificación , Control de Calidad , Radiofármacos/química , Reproducibilidad de los Resultados , Sulfuros/aislamiento & purificación , Medronato de Tecnecio Tc 99m/aislamiento & purificación , Tecnecio Tc 99m Sestamibi/aislamiento & purificación , Azufre Coloidal Tecnecio Tc 99m/aislamiento & purificaciónRESUMEN
BACKGROUND: Pentastarch is used clinically as a plasma volume expander for the management of substantial blood loss. 99mTc labelled pentastarch may be useful as a diagnostic agent in place of 99mTc labelled red blood cells. METHODS: Commercial pentastarch (PS; molecular weight (MW) 240 kDa) was separated according to molecular size by using chromatography, and the fractions were pooled as small (MW 128 kDa), medium (MW 277 kDa) and large (MW 510 kDa) pentastarch. We studied the effect of various physicochemical parameters on the efficiency of radiolabelling with 99mTc and on the stability of the products, and evaluated the biological properties of the 99mTc labelled preparations. RESULTS: We developed an optimised kit formulation containing 3.25 mg pentastarch and 0.13 mg gentisic acid that can be reliably labelled with 99mTc at pH 6.6-8.2 with good stability. In mice, the 99mTc labelled medium pentastarch showed the more favourable blood retention properties (56% of initial blood activity is retained after 3 h) with lower liver levels.
Asunto(s)
Derivados de Hidroxietil Almidón/química , Derivados de Hidroxietil Almidón/farmacocinética , Marcaje Isotópico/métodos , Tecnecio/química , Tecnecio/farmacocinética , Animales , Fraccionamiento Químico , Concentración de Iones de Hidrógeno , Derivados de Hidroxietil Almidón/sangre , Masculino , Tasa de Depuración Metabólica , Ratones , Peso Molecular , Especificidad de Órganos , Tamaño de la Partícula , Radiofármacos/sangre , Radiofármacos/química , Radiofármacos/farmacocinética , Tecnecio/sangre , Distribución TisularRESUMEN
A quality control procedure for 99mTc-IDA complexes based on the use of C18 Sep-pak cartridges is developed and the validation of the procedure presented. C18 Sep-pak cartridges are pretreated by washing with 95% ethanol followed by 10(-3) N hydrochloric acid. A small amount of the 99mTc-IDA complex is applied, washed with 10(-3) N hydrochloric acid and eluted with 95% ethanol. The radiochemical purity values obtained for 99mTc-mebrofenin and 99mTc-disofenin using this Sep-pak procedure are comparable to those obtained using the standard two strip (ITLC-SG/100% methanol, ITLC-SA/20% saline) procedure.
Asunto(s)
Cromatografía en Capa Delgada/métodos , Iminoácidos/análisis , Iminoácidos/química , Compuestos de Organotecnecio/análisis , Compuestos de Organotecnecio/química , Garantía de la Calidad de Atención de Salud/métodos , Dióxido de Silicio/química , Radiofármacos/análisis , Radiofármacos/químicaRESUMEN
UNLABELLED: Over the past several years, investigators in this laboratory and elsewhere have been studying tumor localization by pretargeting with streptavidin and biotin or with avidin and biotin. Despite encouraging results, difficulties related to endogenous biotin and the immunogenicities of streptavidin and avidin have made a search for alternative strategies sensible. Recently, we have considered the use of DNAs and peptide nucleic acids for this purpose because oligomers can have hybridization affinities equivalent to that of biotin for streptavidin or avidin without the associated difficulties. We now report on the use of a morpholino (MORF), another commercially available synthetic oligomer, for pretargeting applications. MORFs support the nitrogenous bases by nonionic phosphorodiamidate linkages and, besides being nuclease resistant, can display good water solubility. METHODS: An 18mer MORF and its 18mer complementary MORF (cMORF) were obtained with a primary amine through a 3-member alkyl linker on the 3' equivalent end. An anti--carcinoembryonic antigen IgG antibody (MN14) was conjugated with MORF, whereas cMORF was conjugated with N-hydroxysuccinimide-mercaptoacetyltriglycine (MAG3) to permit radiolabeling with (99m)Tc. The biodistribution of labeled cMORF was first evaluated in normal CD-1 mice. Subsequently, nude mice bearing LS174T tumors received 50 microg conjugated antibody 48 h before the administration of 1.0 microg (7.4 MBq) (99m)Tc-MAG3-cMORF. Control animals received the labeled cMORF without prior administration of the antibody. A clearing step was not used. RESULTS: Biodistributions in normal mice showed that (99m)Tc-MAG3-cMORF was excreted rapidly through the kidneys, with only 7 percentage injected dose (%ID) remaining within the whole body (excluding urine) at 3 h. In tumor-bearing mice at 24 h, only 11 %ID of the radioactivity remained in the whole body of study animals, and of this amount, 2 %ID/g was in tumor tissue. The sites with the highest %ID were the kidneys, at 4 %ID/g, and the blood, at 0.5 %ID/g; all other organs had <1 %ID/g. At the same time, values for the control animals were 5 %ID (whole body), 0.05 %ID/g (tumor), and 3 %ID (kidneys). All images reflected high uptake in the tumors and low uptake in the normal tissues of the study mice. CONCLUSION: Pretargeting using MORFs was effective in a mouse tumor model.