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1.
Blood ; 132(1): 59-66, 2018 07 05.
Article in English | MEDLINE | ID: mdl-29784643

ABSTRACT

Spatial intratumor heterogeneity is frequently seen in multiple myeloma (MM) and poses a significant challenge for risk classifiers, which rely on tumor samples from the iliac crest. Because biopsy-based assessment of multiple skeletal sites is difficult, alternative strategies for risk stratification are required. Recently, the size of focal lesions (FLs) was shown to be a surrogate marker for spatial heterogeneity, suggesting that data from medical imaging could be used to improve risk stratification approaches. Here, we investigated the prognostic value of FL size in 404 transplant-eligible, newly diagnosed MM patients. Using diffusion-weighted magnetic resonance imaging with background suppression, we identified the presence of multiple large FLs as a strong prognostic factor. Patients with at least 3 large FLs with a product of the perpendicular diameters >5 cm2 were associated with poor progression-free survival (PFS) and overall survival (OS; median, 2.3 and 3.6 years, respectively). This pattern, seen in 13.8% of patients, was independent of the Revised International Staging System (RISS), gene expression profiling (GEP)-based risk score, gain(1q), or extramedullary disease (hazard ratio, 2.7 and 2.2 for PFS and OS in multivariate analysis, respectively). The number of FLs lost its negative impact on outcome after adjusting for FL size. In conclusion, the presence of at least 3 large FL is a feature of high risk, which can be used to refine the diagnosis of this type of disease behavior and as an entry criterion for risk-stratified trials.


Subject(s)
Diffusion Magnetic Resonance Imaging , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/mortality , Adult , Disease-Free Survival , Female , Humans , Male , Middle Aged , Risk Assessment , Risk Factors , Survival Rate
2.
Bioorg Med Chem Lett ; 26(24): 5883-5886, 2016 12 15.
Article in English | MEDLINE | ID: mdl-27866815

ABSTRACT

The aim of this study was to determine the uptake of intravenously administered N-[11CH3]-dimethylaminoparthenolide (DMAPT) into orthotopic 9LSF glioblastoma brain tumors in Fisher 344 rats from positron emission tomography (PET) imaging studies. [11C]methyl iodide (11CH3I) was utilized as a [11C]-labeling reagent to label the precursor methylaminoparthenolide (MAPT) intermediate. From PET imaging studies it was found that brain uptake of N-[11CH3]DMAPT into brain tumor tissue was rapid (30min), and considerably higher than that in the normal brain tissue.


Subject(s)
Glioblastoma/diagnostic imaging , Sesquiterpenes/pharmacokinetics , Animals , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Glioblastoma/pathology , Molecular Structure , Positron-Emission Tomography , Rats , Rats, Inbred F344 , Sesquiterpenes/chemistry , Structure-Activity Relationship
3.
PLoS One ; 7(7): e41863, 2012.
Article in English | MEDLINE | ID: mdl-22860021

ABSTRACT

Diagnosing bone infection in its acute early stage is of utmost clinical importance as the failure to do so results in a therapeutically recalcitrant chronic infection that can only be resolved with extensive surgical intervention, the end result often being a structurally unstable defect requiring reconstructive procedures. [(18)F]-FDG-PET has been extensively investigated for this purpose, but the results have been mixed in that, while highly sensitive, its specificity with respect to distinguishing between acute infection and sterile inflammatory processes, including normal recuperative post-surgical healing, is limited. This study investigated the possibility that alternative means of acquiring and analyzing FDG-PET data could be used to overcome this lack of specificity without an unacceptable loss of sensitivity. This was done in the context of an experimental rabbit model of post-surgical osteomyelitis with the objective of distinguishing between acute infection and sterile post-surgical inflammation. Imaging was done 7 and 14 days after surgery with continuous data acquisition for a 90-minute period after administration of tracer. Results were evaluated based on both single and dual time point data analysis. The results suggest that the diagnostic utility of FDG-PET is likely limited to well-defined clinical circumstances. We conclude that, in the complicated clinical context of acute post-surgical or post-traumatic infection, the diagnostic utility accuracy of FDG-PET is severely limited based on its focus on the increased glucose utilization that is generally characteristic of inflammatory processes.


Subject(s)
Fluorodeoxyglucose F18 , Osteomyelitis/diagnostic imaging , Radiopharmaceuticals , Radius/diagnostic imaging , Staphylococcal Infections/diagnostic imaging , Surgical Wound Infection/diagnostic imaging , Animals , Fluorodeoxyglucose F18/pharmacokinetics , Male , Osteomyelitis/microbiology , Positron-Emission Tomography , Rabbits , Radiopharmaceuticals/pharmacokinetics , Radius/microbiology , Radius/surgery , Staphylococcal Infections/microbiology , Surgical Wound Infection/microbiology
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