Many medical procedures diagnosing the nature of biological tissues, and the functioning of organs including these tissues, require radiation sources that are introduced into, or ingested by, the tissue. Such radiation sources preferably have a half-life of few hours—neither long enough for the radiation to damage the tissue nor short enough for radiation intensity to decay before completing the diagnosis. Such radiation sources are preferably not chemically poisonous. 18F-Fluoride is such a radiation source.
18F-Fluoride has a lifetime of about 109.8 minutes and is not chemically poisonous in tracer quantities. It has, therefore, many uses in forming medical and radio-pharmaceutical products. The 18F-Fluoride isotope can be used in labeling compounds via the nucleophilic fluorination route. One important use is the forming of radiation tracer compounds for use in medical Positron Emission Tomography (PET) imaging. Fluoro-deoxyglucose (FDG) is an example of a radiation tracer compound incorporating 18F-Fluoride. In addition to FDG, compounds suitable for labeling with 18F-Fluoride include, but are not limited to, Fluoro-thymidine (FLT), fluoro analogs of fatty acids, fluoro analogs of hormones, linking agents for labeling peptides, DNA, oligo-nucleotides, proteins, and amino acids.
Several nuclear reactions, induced through irradiation of nuclear beams (including protons, deuterons, alpha particles, . . . etc), produce the isotope 18F-Fluoride. 18F-Fluoride forming nuclear reactions include, but are not limited to, 20Ne(d,α)18F (a notation representing a 20Ne absorbing a deuteron resulting in 18F and an emitted alpha particle), 16O(α,pn)18F, 16O(3H,n)18F, 16O(3H,p)18F, and 18O(p,n)18F; with the greatest yield of 18F production being obtained by the 18O(p,n)18F because it has the largest cross-section. Several elements and compounds (including Neon, water, and Oxygen) are used as the initial material in obtaining 18F-Fluoride through nuclear reactions.
Technical and economic considerations are critical factors in choosing an 18F-Fluoride producing system. Because the half-life of 18F-Fluoride is about 109.8 minutes, 18F-Fluoride producers prefer nuclear reactions that have a high cross-section (i.e., having high efficiency of isotope production) to quickly produce large quantities of 18F-Fluoride. Because the half-life of 18F-Fluoride is about 109.8 minutes, moreover, users of 18F-Fluoride prefer to have an 18F-Fluoride producing facility near their facilities so as to avoid losing a significant fraction of the produced isotope during transportation. Progress in accelerator design has made available sources of proton beams having higher energy and currents.
Systems that produce proton beams are less complex, as well as simpler to operate and maintain, than systems that produce other types of beams. Technical and economic considerations, therefore, drive users to prefer 18F-Fluoride producing systems that use proton beams and that use as much of the power output available in the proton beams. Economic considerations also drive users to efficiently use and conserve the expensive startup compounds.
However, inherent characteristics of 18F-Fluoride and the technical difficulties in implementing 18F-Fluoride production systems have hindered reducing the cost of preparing 18F-Fluoride. Existing approaches that use Neon as the startup material suffer from problems of inherent low nuclear reaction yield and complexity of the irradiation facility. The yield from Neon reactions is about half the yield from 18O(p,n)18F. Moreover, using Neon as the startup material requires facilities that produce deuteron beams, which are more complex than facilities that produce proton beam.
Using Neon as the start-up material, therefore, has resulted in low 18F-Fluoride production yield at a high cost.
Existing approaches that use 18O-enriched water as the startup material suffer from problems of recovery of the unused 18O-enriched water and of the limited beam intensity (energy and current) handling capability of water. Using 18O-enriched water suffers from slower production cycle times as it is necessary to spend relatively long time to collect and dry-up the unused 18O-enriched water before the formed 18F-Fluoride can be collected. Speeding production cycle at the expense of recovering all of the unused 18O-enriched water will increase the cost because of the unproductive loss of the start-up material. Recovering the unused 18O-enriched water is problematic, moreover, because of contaminating by-products generated as a result of the irradiation and chemical processing. This problem has led users to distill the water before reuse and, thus, implement complex distilling devices. These recovery problems complicate the system, and the production procedures, used in 18O-enriched water based 18F-Fluoride generation; the recovery problems also lower the product yield due in part to non-productive startup material loss and isotopic dilution.
Moreover, although proton beam currents of over 100 microamperes are presently available, 18O-enriched water based systems are not reliable when the proton beam current is greater than about 50 microamperes because water begins to vaporize and cavitate as the proton beam current is increased. The cavitation and vaporization of water interferes with the nuclear reaction, thus limiting the range of useful proton beam currents available to produce 18F-Fluoride from water. See, e.g., Heselius, Schlyer, and Wolf, Appl. Radiat. Isot. Vol. 40, No. 8, pp 663-669 (1989), incorporated herein by reference. Systems implementing approaches using 18O-enriched water to produce 18F-Fluoride are complex and difficult. For example, very recent publications (see, e.g., Helmeke, Harms, and Knapp, Appl. Radiat. Isot. 54, pp 753-759 (2001), incorporated herein by reference, hereinafter “Helmeke”) show that it is necessary to use complicated proton beam sweeping mechanism, accompanied by the need to have bigger target windows, to increase the beam current handling capability a of 18O-enriched water system to 30 microamperes. In spite of the complicated irradiation system and target designs, the Helmeke approach has apparently allowed operation for only 1 hour a day.
Using water as the startup material, therefore, has also resulted in low 18F-Fluoride production yield at high cost.
Accordingly, a better, more efficient, and less costly method of producing 18F-Fluoride is needed.