Pharmacokinetic characteristics of 99mTc-Ethylene-l-dicysteine (99mTc-EC)

Background: Ethylenedicysteine-99mTc (99mTc-EC) has been more and more commonly applied in dynamic studies as well as for clearance determinations. However, it was necessary to investigate in detail the pharmacokinetic characteristics of the radiopharmaceutical which may be important for its applicability in assessment of renal function. Results: Kidney images obtained from renoscintigraphy are characterised by excellent quality without visualisation of the organs adjacent to kidneys (liver, spleen). Renoscintigraphic curves demonstrate typical shapes with TMAX and T1/2 values not differing from the corresponding values obtained for other radiopharmaceuticals (99mTc-MAG3, 131I-OIH). In plasma, 99mTc-EC binds with proteins to a considerably lesser degree (c. 1/3) than 131I-OIH (c. 2/3), or 99mTc-MAG3 (> 9/10). No binding of 99mTc-EC with erythrocytes has been demonstrated, whereas 131I-OIH attaches to or penetrates the red blood cells (10-12%). 99mTc-EC is quickly excreted from the organism: 40 min after i.v. injection up to 70% of the administered radiopharmaceutical is found in urine, and at 1 and 1.5 h after the administration 80% and 95%, respectively. The distribution of 99mTc-EC in the organism can be described in a fully satisfactory way by means of an open two-compartment model, which allows this model to be used for clearance determinations. Comparison of the values of renal plasma clearance without collection of urine with the values determined by means of measurement of activity excreted with urine and mean blood concentration over a finite time interval leads to the conclusion that extrarenal plasma clearance of this compound (via the liver?) is negligible and amounts to c. 17 ml/min (5-6% of the total). The obtained correlation between clearance values for 99mTc-EC and 131I-OIH supports the contention that extrarenal excretion rate of 99mTc-EC (through the liver and bile ducts) is lower than the corresponding rates of either 131I-OIH or 99mTc-MAG3. A very close correlation between clearance values for 99mTc-EC and ERPF (131I-OIH clearance) and between their extraction constants (r = 0.91 and 0.92, respectively), allows for the introduction of 99mTc-EC to the assessment of renal function instead of 131I-OIH. Effective dose to the patient from unit activity of 99mTc-EC is comparable with that resulting from administration of other radiopharmaceuticals labelled with 99mTc

A generic model for C-11 labelled radiopharmaceuticals for imaging receptors in the human brain

A large number of rachopharmaceuticals labelled with C-11 (half-time 0.340 h) are being developed for positron emission tomographic studies of different types of receptor in the human brain. For most of these agents, the available biokinetic data are insufficient to construct realistic compound-specific biokinetic models for calculating the internal radiation dose delivered to persons undergoing investigation. A generic model for brain receptor substances that predicts the internal dose with sufficient accuracy for general radiation protection purposes has, therefore, been developed. Biokinetic data for 13 C-11-radiopharmaceuticals used clinically for imaging different brain receptors indicate that, despite differences in chemical structure. their uptake and retention in the human brain and other tissues are broadly similar. The proposed model assumes instantaneous deposition of 5% of the injected radioactivity in the brain, with the remaining radioactivity being rapidly and uniformly distributed throughout all other tissues. Elimination from all tissues is assumed to occur with a half-time of 2 h. It is further assumed that 75% of the injected C-11 is excreted in the urine, and 25% via the gall bladder, with a half-time of 2 h. This model yields all effective dose of 4.5 X 10(-3) mSv MBq(-1), with doses of 3.2 X 10(-2), 1.7 X 10(-2), 8.7 X 10(-3), 5.2 X 10(-3), and 3.8 X 10(-3) mGy MBq(-1) to the urinary bladder, gall bladder, kidneys, brain and ovaries, respectively. These closes are well within the range of those reported using compound-specific models for the radiopharmaceutals studied

Current activities in the ICRP concerning estimation of radiation doses to patients from radiopharmaceuticals for diagnostic use

A Task Group within the ICRP Committees 2 and 3 is continuously working to improve absorbed dose estimates to patients investigated with radiopharmaceuticals. The work deals with reviews of the literature, initiation of new or complementary studies of the biokinetics of a compound and dose estimates. Absorbed dose calculations for organs and tissues have up to now been carried out using the MIRD formalism. There is still a lack of necessary biokinetic data from measurements in humans. More time series obtained by nuclear medicine imaging techniques such as whole-body planar gamma-camera imaging, SPECT or PET are highly desirable for this purpose. In 2008, a new addendum to ICRP Publication 53 was published under the name of ICRP Publication 106 containing biokinetic data and absorbed dose information to organs and tissues of patients of various ages for radiopharmaceuticals in common use. That report also covers a number of generic models and realistic maximum models covering other large groups of substances (e.g. "(123)I-brain receptor substances"). Together with ICRP Publication 80, most radiopharmaceuticals in clinical use at the time of publication were covered except the radioiodine labeled compounds for which the ICRP dose estimates are still found in Publication 53. There is an increasing use of new radiopharmaceuticals, especially PET-tracers and the TG has recently finished its work with biokinetic and dosimetric data for (18)F-FET, (18)F-FLT and (18)F-choline. The work continues now with new data for (11)C-raclopride, (11)C-PiB and (123)I-ioflupan as well as re-evaluation of published data for (82)Rb-chloride, (18)F-fluoride and radioiodide. This paper summarises published ICRP-information on dose to patients from radiopharmaceuticals and gives some preliminary data for substances under review

Radiation Dose to Patients from from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances.

This report provides a compendium of current information relating to radiation dose to patients, including biokinetic models, biokinetic data, dose coefficients for organ and tissue absorbed doses, and effective dose for major radiopharmaceuticals based on the radiation protection guidance given in Publication 60 (ICRP, 1991). These data were mainly compiled from Publications 53 , 80, and 106 (ICRP, 1987, 1998, 2008), and related amendments and corrections. This report also includes new information for 82 Rb-chloride, iodide (123 I, 124 I, 125 I, and 131 I) and 123 Ilabelled 2.-carbomethoxy 3.-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FPCIT). The coefficients tabulated in this publication will be superseded in due course by values calculated using new International Commission on Radiation Units and Measurements/International Commission on Radiological Protection adult and paediatric reference phantoms and Publication 103 methodology (ICRP, 2007). The data presented in this report are intended for diagnostic nuclear medicine and not for therapeutic applications