Effects of chronic immobilization stress on biokinetics and dosimetry of 67Ga in a murine model.

The aim of this work is to determine the effect of chronic immobilization stress on kinetics and dosimetry of 67Ga in a mouse model. A control group (CG) and a stress group (SG), each with 15 mice, were included in the study, and the latter group was subjected to a chronic immobilization stress model 2 h daily for 14 consecutive days. At day 13, 67Ga-citrate was administered intraperitoneally (11.24 ± 0.44 MBq) to each mouse. Then, sets of three mice were obtained sequentially at 24, 36, 48, 60 and 72 h, in which the radionuclide activity was measured with an activity counter. The 67Ga biokinetic data showed a fast blood clearance in the SG, with a mean residence time of 0.06 h. The calculated mean radiation absorbed doses were: liver (2.45 × 10-03 Gy), heart (3.17 × 10-04 Gy) and kidney (1.88 × 10-04 Gy) in the SG. The results show that stress reduced weight gain by approximately 13% and also increased adrenal gland weight by 26%. On the other hand, chronic stress accelerates 67Ga clearance after 24 h compared to normal conditions. It is concluded that murine organisms under chronic immobilization stress have higher gallium-67 clearance rates, decreasing the cumulated activity and absorbed dose in all organs.

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.

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/[99mTc]Tc-HYNIC-DA (Technetium-99m in the core) and [99mTc]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/[99mTc]Tc-HYNIC-DA and [99mTc]Tc-HYNIC-rHDL show instantaneous absorption in kidney, lung, heart and pancreas, with slower absorption in spleen. rHDL/[99mTc]Tc-HYNIC-DA is absorbed more slowly in the intestine, while [99mTc]Tc-HYNIC-rHDL is absorbed more slowly in the liver. The main target organ for rHDL/[99mTc]Tc-HYNIC-DA, which is hydrophobic in nature, is the liver, whereas the kidney is for the more hydrophilic [99mTc]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 99mTc-labeled rHDL are safe from the dosimetric point of view. The dose estimates obtained can be used to adjust the 99mTc-activity to be administered in future clinical trials.