Biokinetics, radiopharmacokinetics and estimation of the absorbed dose in healthy organs due to Technetium-99m transported in the core and on the surface of reconstituted high-density lipoprotein nanoparticles.

Unlabelled: The development of rHDL-radionuclide theragnostic systems requires evaluation of the absorbed doses that would be produced in healthy tissues and organs at risk. Technetium-99m is the most widely used radionuclide for diagnostic imaging, therefore, the design of theragnostic reconstituted high density-lipoprotein (rHDL) nanosystems labeled with Technetium-99m offers multiple possibilities.

Objective: To determine the biokinetics, radiopharmacokinetics and estimate the absorbed doses induced in healthy organs by Technetium-99m transported in the core and on the surface of rHDL.

Methods: Biokinetic and radiopharmacokinetic models of rHDL/[Tc]Tc-HYNIC-DA (Technetium-99m in the core) and [Tc]Tc-HYNIC-rHDL (Technetium-99m on the surface) were calculated from their ex vivo biodistribution in healthy mice. Absorbed doses were estimated by the MIRD formalism using OLINDA/EXM and LMFIT softwares.

Results: rHDL/[Tc]Tc-HYNIC-DA and [Tc]Tc-HYNIC-rHDL show instantaneous absorption in kidney, lung, heart and pancreas, with slower absorption in spleen. rHDL/[Tc]Tc-HYNIC-DA is absorbed more slowly in the intestine, while [Tc]Tc-HYNIC-rHDL is absorbed more slowly in the liver. The main target organ for rHDL/[Tc]Tc-HYNIC-DA, which is hydrophobic in nature, is the liver, whereas the kidney is for the more hydrophilic [Tc]Tc-HYNIC-rHDL. Assuming that 925 MBq (25 mCi) of Technetium-99m, carried in the core or on the surface of rHDL, are administered, the maximum tolerated doses for the organs of greatest accumulation are not exceeded.

Conclusion: Theragnostic systems based on Tc-labeled rHDL are safe from the dosimetric point of view. The dose estimates obtained can be used to adjust the Tc-activity to be administered in future clinical trials.