ABSTRACT
AIM: Technetium-99m 2-methoxy-isobutyl-isonitrile ([99mTc] MIBI) has been successfully used to study patients with multiple myeloma (MM). This tracer is also a substrate for P-glycoprotein (Pgp). Since Pgp overexpression is one of the primary mechanisms of multidrug resistance in MM, the aim of this study was to test whether [99mTc] MIBI could be an index of Pgp overexpression and function in MM and therefore predicts response to chemotherapy. METHODS: Forty patients with MM (12 in stage I, 15 in stage II, and 13 in stage III) showing diffuse bone marrow [99mTc] MIBI uptake were included in the study. All patients underwent whole body scintigraphy at 10 and 60 minutes after i.v. injection of 555 MBq of [99mTc] MIBI. [99mTc] MIBI washout was measured, after decay correction, as: (10 minute counts/pixel minus 60 minute counts/pixel) divided by 10 minute counts/pixel, computed on a region of interest drawn on the thoracic spine (posterior projection), taking care of avoiding heart and splanchnic organs. Disease restaging was performed at a mean time of 32+/-20 months, and patients were considered to be in remission (complete or partial) or to show disease progression on the basis of a complete clinical and hematological evaluation. RESULTS: Patients showing disease progression at restaging (n=26) had higher washout (19.3+/-9.8% vs 12.8+/-6.9%, p<0.05) than patients in remission (n=14). Disease free survival was significantly better in patients with lower washout of [99mTc] MIBI. No differences in therapeutic regimen and stage of disease at admission were found between the 2 groups. When patients treated with melphalan were excluded from the analysis, 87.5% of patients in remission had low washout. CONCLUSIONS: The present study suggests a potential role of [99mTc] MIBI washout in predicting response to chemotherapy in patients with MM.
Subject(s)
Antineoplastic Agents/therapeutic use , Image Interpretation, Computer-Assisted/methods , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/drug therapy , Radioisotope Dilution Technique , Technetium Tc 99m Sestamibi , Disease-Free Survival , Female , Humans , Male , Metabolic Clearance Rate , Middle Aged , Multiple Myeloma/metabolism , Prognosis , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Sensitivity and Specificity , Technetium Tc 99m Sestamibi/pharmacokinetics , Treatment OutcomeABSTRACT
4,5,6-Trichloroguaiacol (4,5,6-TCG) is a recalcitrant organochlorine compound produced during pulp bleaching and a potential environmental hazard in paper mill effluents. We report here the identification by biochemical tests and molecular biological analysis, using 16S ribotyping, of a 4,5,6-TCG-degrading bacterium, identified as a strain of Bacillus subtilis that is most closely related according to the phylogenetic analysis to B. subtilis strain Lactipan (alignment score 99%). Biodegradation of 4,5,6-TCG by this organism in a mineral salts medium was shown to occur only when the inoculum was composed of cells in the stationary phase of growth and to be accelerated by an additional carbon source, such as glucose, sucrose, glycerol or molasses. An additional nitrogen source (as ammonium sulfate) did not affect the rate of 4,5,6-TGC removal. No plasmids were detected in the bacterial cells. This is the first strain of B. subtilis which degrades chlorophenols and shows that 4,5,6-TCG is not degraded by cometabolism and that the gene encoding this characteristic is probably located on the chromosome. The lack of requirement for additional nitrogen source, the ability to enhance biodegradation by adding cheap carbon sources such as molasses, and the fact the trait is likely to be stable since it is encoded on the cell chromosome, are all characteristics that make the organism an attractive possibility for treatment of wastes and environments polluted with organochlorine compounds.
