Proposed specifications for cyclotron-produced ^99mTc-pertechnetate.

Objectives Cyclotron production of ^99mTc is an attractive option to replace or complement the supply of ^99mTc currently sourced from ⁹⁹Mo generators. Unlike generator produced ^99mTc pertechnetate, (GPP), there are no pharmacopeia standards for cyclotron produced pertechnetate (CPP). The purpose of this study was to develop specifications for CPP, to ensure safe clinical use of this product.

Methods GPP USP standards were used to establish CPP specifications, except for radionuclide purity and reagents specific to CPP production. Theoretical simulations were used to determine limits of radionuclide contaminants based on their impact on absorbed radiation dose, and verified experimentally. Validated standard assay methods were developed for rapid determination of radionuclide purity, and chemical purity including determination of non-radioactive Mo and H₂O₂ concentration.

Results A set of specifications was established for the molybdenum target material composition at various energy levels (<20, 20-22 and 22-24 MeV) to ensure that radiation dose would not exceed pure ^99mTc by more than 11%. Rapid assays were developed for radionuclide purity as well as H₂O₂ and Mo breakthrough. Levels of ≤30 ppm for MoO₄^2- and ≤50 ppm for H₂O₂ are proposed and are consistently achieved by current processes. A maximal threshold for high-energy gamma emission has been established for rapid determination of radionuclide purity

Conclusions With the recent demonstration of >30 Ci batch production and imminent clinical trial for CPP, we propose a simple set of specifications for suitable composition of molybdenum target material at various incident proton beam energies. Detailed specifications for the final product (CPP) are also proposed.

Research Support Natural Resources Canada.