ABSTRACT
We herein examined the biological effects of cells treated with (18)F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of (18)F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with two types of (18)F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF). FDG efficiently accumulated in cells, whereas HF did not. To examine the induction of DNA double strand breaks (DSB), we measured the number of foci for 53BP1 that formed at the site of DNA DSB. The results revealed that although radioactivity levels were the same, the induction of 53BP1 foci was stronger in cells treated with (18)F-FDG than in those treated with (18)F-HF. The clonogenic survival of cells was significantly lower with (18)F-FDG than with (18)F-HF. We concluded that the efficient accumulation of (18)F in cells led to stronger biological effects due to more severe cellular lethality via the induction of DNA DSB.
Subject(s)
Fluorine Radioisotopes/adverse effects , Fluorine Radioisotopes/pharmacokinetics , Fluorodeoxyglucose F18/adverse effects , Fluorodeoxyglucose F18/pharmacokinetics , Positron-Emission Tomography/adverse effects , Radiopharmaceuticals/adverse effects , Radiopharmaceuticals/pharmacokinetics , Animals , CHO Cells , Cell Survival/radiation effects , Colony-Forming Units Assay , Cricetinae , Cricetulus , DNA Breaks, Double-Stranded , Dose-Response Relationship, Radiation , Intracellular Fluid/metabolism , Micronucleus TestsABSTRACT
OBJECTIVE: We developed a bubble point test kit and investigated the bubble point test of a 0.22-µm membrane filter used for the sterilizing filtration of [(18)F]FDG, [(11)C]MET and [(11)C]PIB. The bubble point test of the Millex-GS vented filter was often difficult due to air leakage from the vented portion of this filter. Therefore, to close the vented portion of this filter simply and reliably, we investigated the use of various materials. METHODS: The bubble point test of the Millex-GS vented filter was performed by closing the vented portion of this filter with various materials, such as vinyl tape, plastic paraffin film (parafilm), urethane elastomer adhesive mat and polyethylene foam cushion tape. Gradually, the plunger inside a syringe filled with air was pushed down to increase the pressure on the pressure gauge and the bubble point test kit. Simultaneously, the pressure when a continuous stream of air bubbles that appeared out of the 0.22-µm membrane filter was measured as the product-wetted bubble point value. Then, the plunger inside a syringe filled with 10 mL of water was pushed down to wash the 0.22-µm membrane filter. As in the case in the above-mentioned method of measuring the product-wetted bubble point, the water-wetted bubble point value was measured. RESULTS: The use of the polyethylene foam cushion tape and a double clip could easily and reliably prevent air leakage from the vented portion of the Millex-GS vented filter. In the bubble point test of [(18)F]FDG, [(11)C]MET and [(11)C]PIB, the product-wetted bubble point values were 382.7 ± 6.9 kPa, 385.4 ± 6.2 kPa and 351.6 ± 7.6 kPa, respectively. The bubble point ratio was used to determine the minimum product-wetted bubble point value. All results of the product-wetted bubble point test were beyond the minimum product-wetted bubble point value (334.4 kPa ([(18)F]FDG), 334.4 kPa ([(11)C]MET) and 310.3 kPa ([(11)C]PIB)). Then, the water-wetted bubble point values were 396.5 ± 8.3 kPa, 395.8 ± 8.3 kPa and 390.3 ± 7.6 kPa, respectively. All results of the water-wetted bubble point test were beyond the filter manufacturer's minimum bubble point specification (344.8 kPa). CONCLUSIONS: The bubble point test technique using the bubble point test kit was practical for routine quality control tests of PET radiopharmaceuticals.
