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Nuclear Medicine Department
The following highlights the many accomplishments of the Nuclear Medicine Department (NMD) in FY '98:
Research Highlights
Clinical Studies Section
- Continued to collaborate in multiple new protocols using dual x-ray absorptiometry to measure lean body mass, percent fat, and bone density in patients with Cushings Syndrome, Hypoparathyroidism, and insulin resistance, and in obese children.
- Extensively evaluated the use of In-111 octreotide imaging to detect neuroendocrine tumors including gastrinoma and carcinoid tumors. Determined the optimal imaging time post administration (4h).
- Used I-131 lesion dosimetry to determine effective I-131 activity to be administered to patients.
- Measured glomerular filtration rate in pediatric patients to aid in pharmacokinetic estimation of chemotherapy dose.
- Expanded the use of F-18 fluorodeoxyglucose in oncology (two new protocols) and in nononcology applications.
- Collaborators in ten new clinical protocols (1998) from various Institutes.
Imaging Physics Laboratory
- Patent filed with U.S. Patent Office, November, 1997. Patent application describes a novel instrument design for performing positron emission tomography (PET) that overcomes several significant limitations of the technology and may be particularly useful in small animal imaging.
- Investigated and characterized a variety of PET detector modules constructed from Lutetium Silicate Ortho (LSO), GSO, LGSO and Buismuth Germinate Ortho (BGO) scintillators coupled to miniature position-sensitive photomultiplier tubes. This work has lead to the design of a new "phoswich" detector module that will form the basis for a very high performance small animal PET scanner.
- Identified and characterized a previously unrecognized phenomenon that occurs in high performance LSO/PSPMT detector modules that should allow elimination of intercrystal scattered radiation, a primary cause of event mispositioning in PET.
- Completed a prototype pixelated BGO projection/tomographic imaging system for imaging small laboratory animals (e.g., mice) and carried out a detailed analysis of a new data acquisition electronics to service this system. The imaging system is now being used in preliminary small animal studies while work continues to increase system functionality and user friendliness.
- Completed design and benchtop assembly and testing of components for an imaging probe system. This work has included development of custom-made circuit boards for mounting within the handheld probe; human factors design of the probe assembly; and development of the hardware and software for high-speed data acquisition from the probe. The mechanical components of this system are now being fabricated and initial system integration should occur before the end of calendar year 1998.
- Used our small animal-imaging facility and capabilities to carry out small animal studies with various Institutes:
- Conducted imaging studies of the biodistribution of F-18 fluoride after administration directly into the cerebrospinal fluid space of the mouse;
- performed ultra-high resolution brain imaging in a genetically-altered mouse hydocephalus/glioma model;
- performed imaging in genetically-altered mice unable to metabolize glucose in the liver with the intent of showing that this abnormality can be reversed with gene therapy; and
- performed ECG-gated single photon blood pool imaging of the heart in genetically-altered mice exhibiting hypertrophic cardiomyopathy.
Imaging Science Section
- Determined a new way to compensate for "truncation" of single photon emission computerized tomography (SPECT) data (a common problem in SPECT data acquisition). This method involves acquiring a few additional projections, takes very little extra acquisition time, and so is easily implement clinically.
- Presented a new method for analyzing gated cardiac perfusion scans in order to compute global ventricular function simultaneously with measurements of perfusion. The new method is much less sensitive to noise than previously reported techniques, and so is applicable to gated Tl perfusion scans.
- Implemented an iterative algorithm for reconstruction of whole body PET tomograms. NMD found that this algorithm significantly reduced noise, with no reduction in signal, therefore improving the potential for tumor detection in PET fluorodeoxyglucose images. (Results presented orally at SNM.)
- It is common for PET tumor imaging to be performed without attenuation correction. It has not been documented whether this improves or degrades tumor detection. We investigated the signal to noise characteristics of images with and without attenuation correction. We found that except for very peripheral tumors, tumor detectability (based on signal to noise) is improved by attenuation correction. (Results presented orally at SNM.)
- Described and preliminarily evaluated a PET cardiac imaging method that allows simultaneous measurement of myocardial bloodflow and regional myocardial thickening, using N-13 ammonia. (Presented orally at SNM.)
- Investigated the effects of emission contamination on attenuation-corrected cardiac perfusion images. Found that unless corrections are made for this effect, clinically significant errors in perfusion results can occur, especially for same day 10mCi/30mCi perfusion scans.
Nucleic Acids Radiopharmaceuticals
- The methods of Auger-effect-induced DNA breaks analyses were extended to the study of DNA-protein complexes this year. Using the analytical techniques we developed to assay DNA damage produced by Auger-emitters carried by triplex-forming oligonucleotides, we collaborated with investigators in NIDDK and NCI laboratories to answer molecular structural questions about the Rec A-three stranded DNA complex and measured the DNA kinks in the DNA-CRP complex.
Radiolabeled Antibody and Radiochemistry Section
- Developed two novel methods to minimize renal uptake of small radiolabeled antibody fragments.
- Described the pharmacokinetics and similarities of biodistribution between In-111 and Y-90 anti-Tac monoclonal antibody in patients with ATL.
- Performed the preclinical work that serves as the basis to utilize CHX-A DTPA as our chelating agent for monoclonal antibodies to be used in clinical trials.
- Performed preclinical studies that demonstrated circulating sIL-2Ra interferes with tumor targeting of radiolabeled dsFv and developed a strategy to block this interference.
- Developed and characterized a new Tc-99m hepatobiliary imaging agent based on biocytin.