A new radio-HPLC detection system for measuring radioactivity in plasma samples during Positron Emission Tomography [PET] studies was developed. It is based on detecting both the positron and one of the annihilation photons. The system focused on improving the measurement of radioactivity concentrations on an unmetabolized positron emitting a radiopharmaceutical [PER] in the presence of its radioactive metabolites, all containing the same positron emitter. This paper presents a new detection configuration that improves the minimal detectible activity (MDA), simplify the measuring systems and reduces the error caused by the metabolites. The detector is based on a plastic scintillator and a BGO scintillation crystal, that produces different light output spectra for signal and noise events. By summing the positron and the annihilated photon light outputs, different spectra are obtained for the metabolite and for the parent compound tracer and for tracer marked by different positron emitting isotopes. This new detection system can improve quantitative analysis of plasma samples. The spectrum change provides up to a three-fold improvement in sensitivity compared to the currently used detection systems that measure only the annihilation coincidence events. Results showed that for 11C the MDA was improved by approximately 520%. Furthermore, it provides the additional advantage of reliability by providing a method for separating the signal and noise readings from the gross detector readout. Accurate reconstruction algorithm of the signal was achieved over a wide measuring range even when the signal was only 5% of the gross measurement.

It was found that the energy deposited in the cell from each /sup 10/B(n,/spl alpha/) reaction is 2.3 MeV. This represents the total kinetic energy of the alpha particle and the Li ion. The energy deposited in the cell from each /sup 157/Gd(n,/spl gamma/)/sup 158/Gd reaction is 0.045 MeV, due to the Auger electrons. It was found that /spl sim/6 /sup 10/B(n,/spl alpha/) /sup 7/Li reactions were needed at dose of 3.3 MW /spl times/ Minutes to damage the cells to the 10% level of survival. (The dose is expressed in MW-Min units, i.e. reactor power multiplied by irradiation time in minutes, to avoid using various unknown values of RBE.) Because of the high Gd(n,/spl gamma/) cross section, this same level of survival was obtained at 1.8 MW-Min, with 68 /sup 157/Gd(n,/spl gamma/)/sup 158/Gd reactions.

The purpose of our current work is to establish the minimum detection, of indium contrast agent using dual-energy subtraction imaging above and below indium K-edge. Experiments were performed on the X12 and X17B2 beamlines at the National Synchrotron Light Source using the same method but with two different set-ups. Experiments were first carried out on InCl{sub 3} solutions, then on V79 Chinese hamster cells and on BALB/c mice excised tumors, labeled with indium. For each experiment, several layers of Lucite were placed in front of the phantom to ensure a 43 mm thickness, dose to that of a mammography examination. Results were the same on X12 and X17B2. As expected, indium-free materials disappeared on subtracted images (water, steel reference and screw). Indium samples were easily distinguishable for the following concentrations: 10-5-2-1 mg/cm{sup 2}. Smaller concentrations were not clearly distinguishable and we were unable to see cell samples and tumors. To conclude, the lowest concentration we can image is around 1 mg/cm{sup 2}. These results agree with theoretical results. Such results also suggest that indium concentration in both cells and tumors is lower than 0.5 mg/cm{sup 2}. Since the current detection is dose to optimum, we conclude that dual energy subtraction imaging using indium to label tumors cells and tumors is not possible unless the indium uptake is increased by more than an order of magnitude.

The conditions for the possible initiation of clinical trials with neutron capture therapy at a number of locations in the U.S. is reviewed. There are several new technical developments or plans at the Brookhaven Medical Research Reactor (BMRR), the Power Burst Facility (PBF) at INEL, the Massachusetts Institute of Technology Reactor (MITR) and the Georgia Institute of Technology Research Reactor (GTRR). Emphasis is on the development of epithermal beams for the treatment of deepseated tumors with neutron fluxes in between 10(9) to 10(10) n/cm2s. Therapeutic dose gains, defined as the ratio of tumour dose to maximum normal tissue dose in the treatment volume are expected to be between 2 and 4, depending on the degree of suppression of fast neutron dose. Boron concentrations considered in this case in the tumour are around 35 micrograms 10B/g and tumour/normal tissue concentrations are around 10. The compound development throughout three generations is discussed. The compound proposed nowadays, Na2B12H11SH (or BSH), employed in the treatments in Japan, will likely be replaced in the future by analogous of biomolecules being enriched in the tumour by physiological pathways. Examples are p-boronophenylalanine or boronated porphyrius. The most promising solution envisaged would be the employment of tumour cell specific brononated monoclonal antibodies. Finally the mode of therapy is discussed which will likely be based on a fractioned scheme, to achieve optimized results.

Thiouracil and various derivatives are selectively incorporated into the melanin pigment of melanomas during biosynthesis by serving as false melanin precursors. Using the transplantable Harding-Passey melanoma carried in BALB/c mice, we have extended our previous studies with sulfur-35 (35S) thiouracil. The persistence of high levels of [35S]thiouracil in tumor for periods of up to 2 wk has been demonstrated; during this time the drug content in normal tissues returned to near background levels. The variety of iodine isotopes available makes iodothiouracil a particularly promising melanoma-localizing agent. Tumor uptake and biodistribution of [35S]thiouracil and iodothiouracil (both iodine-127 (127I) and iodine-125 (125I) labeled) have been compared and were found to be essentially the same. The selectivity of [125I]thiouracil for melanoma has been qualitatively demonstrated by autoradiography of whole-body sections and quantitated by analysis of tumor and selected tissues. Iodothiouracil was also shown to localize in remote secondary metastases using a metastatic variant of the Harding-Passey melanoma currently being developed in our laboratory. These studies confirm the melanoma localizing capabilities of an iodinated thiouracil, and therefore the potential of using iodinated thiouracil derivatives for diagnosis and therapy of melanotic melanomas.