The 2006 Henry N. Wagner Lecture: Of mice and men (and positrons)--advances in PET imaging technology.

There have been major advances in PET technology that cumulatively have helped improve image quality, increased the range of applications for PET, and contributed to the more widespread use of PET. Examples of these technologic advances include whole-body imaging, 3-dimensional imaging, new scintillator materials, iterative reconstruction algorithms, combined PET/CT, and preclinical PET. New advances on the immediate horizon include the reintroduction of time-of-flight PET, which takes advantage of the favorable timing properties of newer scintillators; the integration of PET and MRI scanners into a dual-modality imaging system; and the possibility of further significant improvements in spatial resolution in preclinical PET systems. Sensitivity remains a limiting factor in many PET studies. Although, conceptually, huge gains in sensitivity are still possible, realizing these gains is thwarted largely by economic rather than scientific concerns. Predicting the future is fraught with difficulty; nonetheless, it is apparent that ample opportunities remain for new development and innovation in PET technology that will be driven by the demands of molecular medicine, notably sensitive and specific molecular diagnostic tools and the ability to quantitatively monitor therapeutic entities that include small molecules, peptides, antibodies, nanoparticles, DNA/RNA, and cells.     

Release of soluble transferrin receptor from the surface of human leukemic HL60 cells

Information regarding transferrin (Tf) receptor degradation is largely incomplete. HL60 cells were shown to release to their growth medium a Tf-binding protein which could be immunoprecipitated by anti-Tf receptor monoclonal antibodies (MoAbs) B3/25 and OKT9. Soluble Tf receptor was detected in the medium within one hour of replating of cells, and its release was inhibited at 4 degrees C. The affinity of Tf for the soluble receptor released by cells (kd = 2.3 x 10(-10) mol/L) was slightly lower than its affinity for the detergent-solubilized cellular receptor (kd = 1.2 x 10(-10) mol/L). 125I-Tf internalized and released by cells subsequently bound to Tf receptor released by the same cells, and soluble Tf receptor in the conditioned medium (CM) inhibited 125I-Tf binding to intact cells. The soluble Tf receptor isolated from the CM was smaller (78,000 daltons) than the cell surface receptor (94,000 daltons) when analyzed by gel electrophoresis under reducing conditions. Isolated cell membranes readily released soluble receptor; however, this release could be blocked by protease inhibitors. The soluble Tf receptor may represent the extracytoplasmic domain of the cellular Tf receptor released from the surface of HL60 cells through proteolytic cleavage by a membrane-based protease.     

3D PET using a conventional multislice tomograph without septa

A conventional multislice positron emission tomography scanner was modified to operate without interplane septa to evaluate its performance in collecting and reconstructing data in a three-dimensional (3D) format, thereby significantly increasing system sensitivity. A 3D filtered backprojection algorithm was implemented and tested, using both computer simulations and phantom measurements. No artifacts were apparent in the test images, although the algorithm was shown to lead to a 11% degradation in transaxial resolution in the outer planes. Following septa removal, sensitivity was found to increase by a factor of 7 with an increase in scatter fraction from 16 to 41%. Axial resolution degraded from 6.9 to 7.7 mm full width at half maximum at the center of the field of view. The maximum count rate without septa was 2.4 x 10(5) cps, at a concentration of 0.4 microCi/ml, compared with 1.3 x 10(5) cps at 1.5 microCi/ml with septa. Brain studies were performed with volunteers using 18F-fluorodeoxyglucose, 18F-fluorodopa, and H2 15O to compare noise-equivalent count rates and qualitatively assess image quality over a wide range of imaging conditions.