Pilot Study: PET-CT Animal Model for Surveillance of Embedded Metal Fragments

This pilot study will determine the sensitivity and specificity of small animal 18F-flouro-2-deoxy-D-glucose (FDG) Positron Emission Tomography – Computed Tomography (PET-CT) in identifying metabolic changes and primary stage tumors in muscle tissue surrounding a heavy metal tungsten alloy and  compare this imaging to traditional x-ray. Male Fischer 344 rats are randomly assigned to one of two groups.  One group implanted  with weapons grade heavy metal tungsten alloy (HMTA) pellets and the other is implanted with the inert metal tantalum (Ta) as a control. Because shrapnel wounds that would be suffered by military personnel during a conflict are being simulated, the pellets must be implanted into the rat. Advances in surgical techniques have allowed the implantation of the metal pellets without the cutting of muscle tissue. All animals are anesthetized for implantation and provided analgesic postoperatively as needed. Animals have a series of one to six x-rays and PET-CT scans over 16 weeks. Rodents from each group are sacrificed for histopathology of tissue around the implants at each of six time points. Tissue biomarkers of myoglobin and desmin are compared to determine muscle tissue differentation around the embedded metals. Radiologists blinded to the rodent groups interpret the images.  Imaging results are compared between groups and imaging types. FDG uptake on PET-CT scans is quantified using the standard unit value. Imaging data will be compared between groups and overtime using repeated measures analysis of variance (ANOVA).  Sensitivity is the proportion of disease positive rats that test positive.  Specificity is the proportion of disease negative rats that test negative. Significance level will be set at 5% for each test. It is hypothesized that increased uptake of FDG will occur in areas of chronic inflammation. It is also hypothesized that the PET-CT images will show changes in the region of interest before changes appear on x-ray.

Relevance: The current surveillance program of service members with retained mental fragments uses traditional two dimensional x-ray imaging to detect changes in the metal fragments. X-ray does not capture soft tissue in images or cellular and metabolic activity. Radiolabelled tracers with PET-CT imaging can be a sensitive method by which to examine abnormal changes in tissue associated with the progression of cancers.Early detection of these changes can provide valuable time for intervention and treatment.

Final Report is available on NTRL: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB2013103...