Comparison of three cold kit reconstitution techniques for the reduction of hand radiation dose.

In the performance of conventional nuclear pharmacy work, personnel usually receive the highest hand radiation dose during reconstitution of 99Tcm-labelled radiopharmaceuticals. This study was conducted to compare the hand radiation doses incurred during the preparation of 99Tcm-labelled radiopharmaceuticals using three different reconstitution procedures: (1) the standard reconstitution method (i.e. withdrawing 99Tcm activity and normal saline [NS] into the same syringe before adding to the cold kit) (standard); (2) an alternative reconstitution procedure using two syringes to add normal saline separately before 99Tcm activity to the cold kit (NS/Tc); and (3) a standard reconstitution procedure using a robotic system (Amercare Syringe Fill Station, model NuMed SFS 3a, Amercare Ltd, Oxon, UK) (robot). Radiation doses were monitored by thermoluminescent dosimeters (Landauer Inc., Glenwood, IL, USA) on the base of the fourth finger (i.e. ring finger) of the non-dominant hand and on the mid-portion of the second finger (i.e. index finger) of the dominant hand. Three sets of ring badges were measured for each procedure, with 10 stimulated or real reconstitutions per set. Two different radiopharmaceutical kits were evaluated: 99Tcm-MDP, as it is the most frequently used radiopharmaceutical in the majority of nuclear medicine departments (all three reconstitution methods; i.e. standard, NS/Tc and robot), and 99Tcm-sestamibi, as it is not only reconstituted with the highest amount of radioactivity but is also the most frequently dispensed radiopharmaceutical in our laboratory (standard and robot). All kits were prepared from an elution vial containing a standardized amount of 99Tcm activity (i.e. 104.4 +/- 3.6 GBq). To each of the cold MDP and sestamibi kits, 20.7 +/- 1.2 GBq and 44.2 +/- 0.7 GBq of 99Tcm activity were added, respectively. Average accumulated radiation doses for 10 reconstitutions to the fingers (non-dominant/dominant) for the preparations of 99Tcm-MDP were as follows: 14.2 +/- 0.9 mSv/2.8 +/- 0.8 mSv (standard), 10.0 +/- 0.6 mSv/2.7 +/- 0.2 mSv (NS/Tc), and 0.6 +/- 0.1 mSv/1.3 +/- 0.1 mSv (robot). For 99Tcm-sestamibi, the average accumulated radiation doses for 10 reconstitutions to the fingers (non-dominant/dominant) were 6.7 +/- 0.7 mSv/4.6 +/- 0.5 mSv (standard) and 1.1 +/- 0.1 mSv/3.1 +/- 0.4 mSv (robot). When compared to the standard reconstitution method, our results show that the NS/Tc method slightly reduced radiation dose to the non-dominant hand, without any significant reduction for the dominant hand. However, the robot has proved to be the most effective method to considerably reduce radiation dose to both hands. A robotic system should be a useful ALARA (as low as reasonably achievable) tool to prepare other high-activity 99Tcm-labelled radiopharmaceuticals, as well as therapeutic and PET radiopharmaceuticals.

Effects of alternative reconstitution procedures on the labelling efficiency and in vitro stability of 99Tcm-labelled radiopharmaceuticals.

Adding normal saline (NS) separately before 99Tcm-sodium pertechnetate to MDP cold kits has been shown to reduce substantially the radiation dose to the hand. A similar dose reduction will probably prove to be valid with the preparation of most other 99Tcm-labelled radiopharmaceuticals. However, it is unknown how this altered reconstitution procedure may affect the labelling efficiency and in vitro stability of the 99Tcm-labelled radiopharmaceuticals. We have evaluated the effects on the labelling efficiency and in vitro stability of 99Tcm-labelled MDP, mertiatide and sestamibi reconstituted with three different methods: adding normal saline before 99Tcm activity (NS/Tc); adding 99Tcm activity before normal saline (Tc/NS); and the standard reconstitution method of adding both 99Tcm activity and normal saline together. The labelling efficiency and in vitro stability were evaluated by measuring the radiochemical purity of each radiopharmaceutical tested at 0, 1, 3, 6, 12 (except 99Tcm-MDP) and 24 h after reconstitution. For 99Tc-mertiatide, there was a very slight difference in the labelling efficiency, mostly due to the Tc/NS method being approximately 0.29% lower across time post-reconstitution than the standard method. For 99Tcm-labelled MDP and sestamibi, there were no differences between the three methods in terms of labelling efficiency and in vitro stability. In conclusion, both alternative methods (i.e. NS/Tc and Tc/NS) appear not to have any detrimental effect on the labelling efficiency and in vitro stability of the 99Tcm-labelled radiopharmaceuticals that we tested. However, of the two alternative kit reconstitution methods, we recommend the NS/Tc method, since it may reduce the hand radiation dose.

Faster and easier radiochemical purity testing for [125I]sodium iothalamate.

A previous method for determination of the radiochemical purity (RCP) value of [125I]sodium iothalamate uses two paper strips and solvents (total developing time is approximately 2.5 h). To simplify and shorten the RCP testing procedure, our laboratory has developed a single-strip chromatography method that not only distributes free 125I and [125I]sodium iothalamate to different relative front (Rf) locations, but is also faster and easier to perform. RCP of [125I]sodium iothalamate was determined with the use of a 10-cm instant thin-layer chromatography strip impregnated with polysilicic acid gel (ITLC-SA) as the solid phase, and a mobile phase of 2-butanol:acetic acid:water (140:2.5:70, v/v). By using autoradiography and counting the strip segments in a gamma counter, our results indicated that free 125I migrated to Rf = 0.89-1.00 while the [125I]sodium iothalamate moved to Rf = 0.44-0.67. The total developing time for the single-strip ITLC-SA system was approximately 1 h.

Optimal conditions of 99mTc eluate for the radiolabeling of 99mTc-sestamibi.

Our nuclear pharmacy has reported that a failed radiochemical purity (RCP) (i.e., RCP < 90%) of 99mTc-sestamibi may be associated with the use of a first elution at later stages from a long-ingrowth time (i.e., > or = 72 h) wet-column generator. The primary purpose of this study was to evaluate the effects of 99mTc eluates from wet- and dry-column generators on the RCP of 99mTc-sestamibi under the above conditions. RCP values were found to be measurably higher and kit failure rates lower with the use of dry-column generator eluate. Using a dry-column generator eluate, Cardiolite kits were prepared with 11.10 GBq of 99mTc at 3, 4, and 5 h postelution and 5.55 GBq at 6, 10, 11, and 12 h postelution. Our data suggest that when 11.10 GBq of 99mTc from a dry-column generator with > or = 72-h ingrowth was used to prepare 99mTc-sestamibi, kit failure started to occur using 99mTc eluate at approximately 4 h postelution. When 5.55 GBq was used to reconstitute the kit, RCP failure began to occur using 99mTc eluate approximately 10 h postelution and wet-column generators; the failure rate can be reduced even further by avoiding the addition of high activities of 99mTc and long elution times.

Generator eluate effects on the labeling efficiency of 99mTc-sestamibi.

Our nuclear pharmacy noted that 99mTc-sestamibi kits sometimes failed radiochemical purity (RCP) testing (i.e., RCP < 90%). All failed kits had been prepared with eluate from a newly arrived generator (ingrowth time > or = 72 h) which had been eluted > or = 6 h before the kit failure. The effects of 99mTc activity and eluate volume were then investigated to help explain the reason for the low RCP values. Our results demonstrated that higher failure rates of the 99mTc-sestamibi kits were noted when higher activities of 99mTc eluates were added, and the higher failure rates of the kits were associated with lower RCP values. In addition, higher kit failure rate and lower RCP values of the 5.55-GBq kits at 12 h postelution in comparison with the 11.1-GBq kits at 6 h (same eluate volume) indicated that the 99mTc activity and volume had a less detrimental effect on the 99mTc-sestamibi kit preparation than the 99mTc eluate age. The kit failures might be explained by the higher amount of 99mTc and the production of the free radicals during the long ingrowth time prior to generator elution. In conclusion, the use of a first elution from a long-ingrowth time generator at a later stage (i.e., 11.1 GBq at 6 h and 5.55 GBq at 12 h postelution) in preparation of a 99mTc-sestamibi kit is associated with a high rate of kit failure and should therefore be avoided.

Modified radioiodination and quality control methods for [125I]sodium iothalamate.

[125I]Sodium iothalamate can be prepared by the isotope-exchange method with the use of a contrast medium preparation (i.e. iothalamate sodium injection, USP, 80%). The initial isolation and purification of iothalamate from the contrast medium solution for radioiodination is tedious and time-consuming (i.e. 1 1/2 h for purification and overnight for drying). The new method uses iothalamic acid to replace iothalamate sodium injection as a starting material and reduces the heating time and multiple acid-washing steps during radioiodination to expedite the radiolabelling process. The radiochemical purity (RCP) of [125I]sodium iothalamate obtained from the new method was 98.9 +/- 1.3% (n = 30) versus RCP value of 99.2 +/- 1.0% (n = 25) from the old method with no significant differences between the two groups of RCP values. An RCP chromatographical system to separate and migrate the radiochemical species of [125I]sodium iothalamate from the origin is described in this paper.