Proton Induced Reactions on Molybdenum: Implications for Medical ^99mTc Production

Recent shortages in the supply of ^99mTc, a critical medical isotope, have prompted research into an alternative production method,¹⁰⁰Mo(p,2n), which could exploit an existing network of medical cyclotrons. One complication of this method, however, is the unavoidable co-production of other Tc isotopes which will affect both diagnostic imaging quality and radiation dosimetry. Currently, the production of these isotopes is being evaluated with statistical nuclear physics models, whose accuracy is highly dependent on input model parameters. The objective of this study is to provide experimental cross section measurements that can be used to predict Tc production in thick yield targets, as well as guide the choice of these model parameters.

In this thesis, production cross sections for (p,x) reactions from all stable Mo species were measured using the charged particle activation method. We report the majority of the cross sections for production of Tc, Mo, and Nb isotopes with half-lives between four minutes and ninety-one days. While not directly relevant to radiopharmaceuticals, Nb and Mo production will have an impact on target composition after repeated recycling and dosimetry in the case of incomplete chemical purification.

From these measurements, a set of input parameters for a TALYS calculated Hauser Feshbach model were identified as best reproducing the experimental measurements. Using this experimentally guided model, we have estimated yields for various target impurity profiles. These yields were combined with dosimetry calculations from the literature to estimate the feasibility of regional production based on the produced ^99mTc specific activity and radionuclidic purity as a function of incident energy, target thickness, target composition, and distribution time.

This analysis demonstrates that the specific activity of cyclotron produced ^99mTc-pertechnetate will likely always be below---in certain conditions substantially---than that from a typical (24 hour) generator elution from the current reactor production method, and that the specific activity will depend critically on target processing and distribution time and to a limited extent on incident proton energy. Target composition will likely play a minor role. The continued path forward for cyclotron production of ^99mTc will necessitate further study on the impact of low specific activity on labeling efficiency for currently available kits.

The results of this study also suggest that radionuclidic purity (and similarly, the expected patient dose increase relative to a procedure with ^99mTc from the current reactor production method) will depend on subtle difference in the isotopic impurity profile. Specifically ^94-97Mo content in the target will contribute to a large dose increase. The unique lifetimes, production cross sections, and dosimetry of each Tc isotope make a “one-size fits all” approach to finding an optimal set of irradiation parameters impossible. Due to this highly individual nature, regulatory limits will most likely be imposed for individual Tc species, making accurate estimation from experimental measurements critical. Finally, our study suggests that given the current Mo recovery rates in target processing, build-up of trace contaminants in the target is likely not a significant issue.

Ultimately, the feasibility of this method of production will depend on currently non-existent regulatory limits. Our work suggests that a significant factor in meeting these potential limits will be the availability of highly enriched ¹⁰⁰Mo with minimal (<0.02%) ^94-97Mo content and the use of short (~3 hour) bombardment duration.