Carrier Added (CA) and Non-Carrier Added (NCA)
The production of 177-Lu
177-Lu is a fully synthetic isotope.
there are 2 ways to produce 177-Lu:
The direct route –
by irradiation of 176-Lu enriched target with thermal neutrons in a nuclear reactor.
Following irradiation, the target material is simply dissolved in diluted acid, dispensed and steam sterilized.
The final products contain up to 0.07% 177m-Lu and is referred to as Carrier Added (CA).
This route of production is highly efficient because of its simplicity, with only a 5% material loss in the process.
176-Lu is a low-cost starting material and the simplicity of the production process brings more competition to the market.
However, the presence of 177m-Lu with 160 days half-life can create a radiation safety challenge in radioactive waste management.
The indirect route –
by irradiating enriched 176-Yb (Ytterbium) target with thermal neutrons in a nuclear reactor.
Following irradiation, the target material undergoes a separation that purifies the 177-Lu by removing the 176-Yb.
After separation the bulk solution is dispensed and steam sterilized.
The final product does not contain 177m-Lu and is referred to as Non-Carrier Added (NCA).
The cost of producing 177-Lu via the indirect route is substantially more expensive than via the direct route due to the cost of starting material (176-Yb) and since the manufacturing process is challenging as it requires to separate micro amounts of 177-Lu from macro amounts of 176-Yb with a 25% material loss causing a significantly lower efficiency in production.
Isotopia have developed a unique separation method that reduced the material loss to 10%.
NCA 177-Lu is preferred by the environmental authorities because no long-lived isotope impurities (177m-Lu) exist in the end product.
From a clinical standpoint there is no published difference between the Carrier Added and the Non-Carrier Added 177-Lu.
Why 177-Lu is gaining popularity in radioligand therapy (RLT).
177-Lu is a medium-energy ß-emitter (490 keV) with Long physical half-life of 6.7 days, which is helpful for synthesis and transport, and average beta – particle range in soft tissue of 670 nm and maximal tissue penetration of 1-2 mm. Another benefit of 177-Lu is that it produces low energy gammas (113 keV, 208 keV), suitable for imaging purposes, allowing biodistribution and excretion kinetics to be monitored and calculating dosimetry with SPECT-CT. 177-Lu has favorable chemistry for chelation, therefore it is gaining popularity for therapy applications.