Coupling Unique Therapeutic Features with Emerging Bioanalytical Tools: Application to Radioligand Therapies

Radioligand Therapeutics (RLTs) are one of several targeted treatment modalities used to reimagine cancer care. RLTs are used for diagnostic imaging or therapy, depending which radioactive metal is present, with the same base compound being used to either diagnose (Ga-68) or treat (Lu-177) patients.
After confirming RLT binding to the target tumor, decision-making in the discovery phase is accelerated using non-radioactive metal to assess in vivo metabolism of intact RLT and excretion of both parent and metal containing metabolites. With the goal to minimize off-target radiation exposure, drug candidates that demonstrate in vivo stability in blood and rapid clearance in urine are prioritized.
The inclusion of metal into the therapeutic opens the possibility for non-traditional detection methods, namely Inductively Coupled Plasma Mass Spectrometry (ICP-MS). By altering the configuration of the ICP-MS setup, detection of both total metal and individual parent and metabolite peaks is possible. When combined with data from more traditional LC-MS/MS or ligand binding approaches, a rich data set is acquired. This guides prioritization of compounds with the desired ADME properties for further development.