Molybdenum (₄₂Mo) has 39 known isotopes, ranging in atomic mass from 81 to 119, as well as four metastable nuclear isomers. Seven isotopes occur naturally, with atomic masses of 92, 94, 95, 96, 97, 98, and 100. All unstable isotopes of molybdenum decay into isotopes of zirconium, niobium, technetium, and ruthenium.^[5]

Molybdenum-100, with a half-life of approximately 8.5×10¹⁸ y, is the only naturally occurring radioisotope. It undergoes double beta decay into ruthenium-100. Molybdenum-98 is the most common isotope, comprising 24.14% of all molybdenum on Earth. Molybdenum isotopes with mass numbers 111 and up all have half-lives of approximately .15 s.^[5]

Molybdenum-99 is produced commercially by intense neutron-bombardment of a highly purified uranium-235 target, followed rapidly by extraction.^[7] It is used as a parent radioisotope in technetium-99m generators to produce the even shorter-lived daughter isotope technetium-99m, which is used in approximately 40 million medical procedures annually. A common misunderstanding or misnomer is that ⁹⁹Mo is used in these diagnostic medical scans, when actually it has no role in the imaging agent or the scan itself. In fact, ⁹⁹Mo co-eluted with the ^99mTc (also known as breakthrough) is considered a contaminant and is minimised to adhere to the appropriate USP (or equivalent) regulations and standards. The IAEA recommends that ⁹⁹Mo concentrations exceeding more than 0.15 µCi/mCi ^99mTc or 0.015% should not be administered for usage in humans.^[8] Typically, quantification of ⁹⁹Mo breakthrough is performed for every elution when using a ⁹⁹Mo/^99mTc generator during QA-QC testing of the final product.

There are alternative routes for generating ⁹⁹Mo that do not require a fissionable target, such as high or low enriched uranium (i.e., HEU or LEU). Some of these include accelerator-based methods, such as proton bombardment or photoneutron reactions on enriched ¹⁰⁰Mo targets. Historically, ⁹⁹Mo generated by neutron capture on natural isotopic molybdenum or enriched ⁹⁸Mo targets was used for the development of commercial ⁹⁹Mo/^99mTc generators.^[9][10] The neutron-capture process was eventually superseded by fission-based ⁹⁹Mo that could be generated with much higher specific activities. Implementing feed-stocks of high specific activity ⁹⁹Mo solutions thus allowed for higher quality production and better separations of ^99mTc from ⁹⁹Mo on small alumina column using chromatography. Employing low-specific activity ⁹⁹Mo under similar conditions is particularly problematic in that either higher Mo loading capacities or larger columns are required for accommodating equivalent amounts of ⁹⁹Mo. Chemically speaking, this phenomenon occurs due to other Mo isotopes present aside from ⁹⁹Mo that compete for surface site interactions on the column substrate. In turn, low-specific activity ⁹⁹Mo usually requires much larger column sizes and longer separation times, and usually yields ^99mTc accompanied by unsatisfactory amounts of the parent radioisotope when using γ-alumina as the column substrate. Ultimately, the inferior end-product ^99mTc generated under these conditions makes it essentially incompatible with the commercial supply-chain.

In the last decade, cooperative agreements between the US government and private capital entities have resurrected neutron capture production for commercially distributed ⁹⁹Mo/^99mTc in the United States of America.^[11] The return to neutron-capture-based ⁹⁹Mo has also been accompanied by the implementation of novel separation methods that allow for low-specific activity ⁹⁹Mo to be utilized.