Differentiation between chemo- and radiotoxicity of 137Cs and 60Co on Lemna minor.

The uptake and effects of stable Cs and Co on L.minor were extensively studied, together with the effects of gamma radiation using a 137Cs or 60Co source. Innovative is that we combined external irradiation (from 137Cs or 60Co sources) with the direct uptake of certain amounts of stable Cs or Co to simulate the impact of the same mass of a radioisotope compared with that of the stable element. Such approach allows to differentiate between chemo- and radiotoxicity of 137Cs or 60Co, permitting to study the 137Cs and 60Co uptake by L. minor without using high concentrations of these elements in solution. Our results indicate that radiotoxicity of both 137Cs and 60Co has a greater importance compared to their chemotoxicity. This was also supported by the independent action and concentration addition concepts. Both concepts resulted in a good prediction of the dose-response curve of the combination exposure. The maximal removal of 137Cs or 60Co per gram dry matter of L. minor was lower compared with the removal of the corresponding stable isotope. The toxicity of 60Co was higher compared to 137Cs based on EC50 values and uptake data. With respect to the effects on photosynthetic pigments, starch and soluble sugars contents, only starch increased in a concentration- and dose-dependent manner.

A Realistic Multiregion Mouse Kidney Dosimetry Model to Support the Preclinical Evaluation of Potential Nephrotoxicity of Radiopharmaceutical Therapy.

Suborgan absorbed dose estimates in mouse kidneys are crucial to support preclinical nephrotoxicity analyses of α- and ß-particle-emitting radioligands exhibiting a heterogeneous activity distribution in the kidneys. This is, however, limited by the scarcity of reference dose factors (S values) available in the literature for specific mouse kidney tissues. Methods: A computational multiregion model of a mouse kidney based on high-resolution MRI data from a healthy mouse kidney was developed. The model was used to calculate S values for 5 kidney tissues (cortex, outer and inner stripes of outer medulla, inner medulla, and papilla and pelvis) for a wide range of ß- or α-emitting radionuclides (45 in total) of interest for radiopharmaceutical therapy, using Monte Carlo calculations. Additionally, regional S values were applied for a 131I-labeled single-domain antibody fragment with predominant retention in the outer stripe of the renal outer medulla. Results: The heterogeneous activity distribution in kidneys of considered α- and low- to medium-energy ß-emitters considerably affected the absorbed dose estimation in specific suborgan regions. The suborgan tissue doses resulting from the nonuniform distribution of the 131I-labeled antibody fragment largely deviated (from -40% to 57%) from the mean kidney dose resulting from an assumed uniform activity distribution throughout the whole kidney. The absorbed dose in the renal outer stripe was about 2.0 times higher than in the cortex and in the inner stripe and about 2.6 times higher than in inner tissues. Conclusion: The use of kidney regional S values allows a more realistic estimation of the absorbed dose in different renal tissues from therapeutic radioligands with a heterogeneous uptake in the kidneys. This constitutes an improvement from the simplistic (less accurate) renal dose estimates assuming a uniform distribution of activity throughout kidney tissues. Such improvement in dosimetry is expected to support preclinical studies essential for a better understanding of nephrotoxicity in humans. The dosimetric database has added value in the development of new molecular vectors for radiopharmaceutical therapy.

Assessment of mouse-specific pharmacokinetics in kidneys based on 131I activity measurements using micro-SPECT.

BACKGROUND: In order to acquire accurate drug pharmacokinetic information, which is required for tissue dosimetry, micro-SPECT must be quantitative to allow for an accurate assessment of radioligand activity in the relevant tissue. This study investigates the feasibility of deriving accurate mouse-specific time-integrated drug pharmacokinetic data in mouse kidneys from activity measurements using micro-SPECT. METHODS: An animal experiment was carried out to evaluate the accuracy of 131I activity quantification in mouse kidneys (mean tissue volume of 0.140 mL) using a micro-SPECT system against conventional ex vivo gamma counting (GC) in a NaI(Tl) detector. The imaging setting investigated was that of the mouse biodistribution of a 131I-labelled single-domain antibody fragment (sdAb), currently being investigated for targeted radionuclide therapy of HER2-expressing cancer. SPECT imaging of 131I 365-keV photons was done with a VECTor/CT system (MILabs, Netherlands) using a high-energy mouse collimator with 1.6-mm-diameter pinholes. For both activity quantification techniques, the pharmacokinetic profile of the radioligand from approximately 1-73 h p.i. was derived and the time-integrated activity coefficient per gram of tissue (ã/M) was estimated. Additionally, SPECT activity recovery coefficients were determined in a phantom setting. RESULTS: SPECT activities underestimate the reference activities by an amount that is dependent on the 131I activity concentration in the kidney, and thus on the time point of the pharmacokinetic profile. This underestimation is around - 12% at 1.5 h (2.89 MBq mL-1 mean reference activity concentration), - 13% at 6.6 h (149 kBq mL-1), - 40% at 24 h (17.6 kBq mL-1) and - 46% at 73 h (5.2 kBq mL-1) p.i. The ã/M value estimated from SPECT activities is, nevertheless, within - 14% from the reference (GC) ã/M value. Furthermore, better quantitative accuracy (within 2% from GC) in the SPECT ã/M value is achieved when SPECT activities are compensated for partial recovery with a phantom-based recovery coefficient of 0.85. CONCLUSION: The SPECT imaging system used, together with a robust activity quantification methodology, allows an accurate estimation of time-integrated pharmacokinetic information of the 131I-labelled sdAb in mouse kidneys. This opens the possibility to perform mouse-specific kidney-tissue dosimetry based on pharmacokinetic data acquired in vivo on the same mice used in nephrotoxicity studies.

Intercomparison and performance assessment of radionuclide calibrators used in nuclear medicine departments in Serbia.

The purpose of this work is to assess accuracy and compare the performance of radionuclide calibrators (RNCs) used in nuclear medicine departments in Serbia. Testing of the RNCs included verification of measurement accuracy, as well as analysis of routinely used quality control protocols, by using the certified radioactivity standards (57Co, 137Cs). RNCs performances were assessed with 99mTc through comparison of reference value for radionuclide activity and RNC measurements. Results of the intercomparison revealed that RNCs, 15 in total, are accurate within 10% in vial geometry and within 15% in syringe geometry. Most of them showed similar performance. The results revealed that container geometry is an important influencing parameter in the accuracy of activity measurement. Obtained results indicate a need for regular calibration and implementation of Quality Control program in order to achieve and maintain the accuracy of activity measurements in nuclear medicine.