Bioluminescence Image as a Quantitative Imaging Biomarker for Preclinical Evaluation of Cryoablation in a Murine Model.

PURPOSE: To employ bioluminescence imaging (BLI) as a quantitative imaging biomarker to assess preclinical evaluation of cryoablation in a murine model. MATERIALS AND METHODS: In vitro, Colon26-Luc (C26-Luc) cells were seeded at 6 different concentrations in 35-mm dishes. These were divided into 6 groups: group 0 (G0), a control group without treatment; and groups 1-5 (G1-G5) according to the number of freeze-thaw cycles, with each cycle consisting of freezing at -80°C for 10 min followed by thawing at room temperature for 5 minutes. BLI and flow-cytometric analysis were performed after cryotherapy. In vivo, 20 tumor-bearing mice with C26-Luc cells were divided into 4 groups: group 0 (G0), a control group; and groups 1-3 (G1-G3) according to the number of freeze-thaw cycles. Each cryoablation procedure was performed for 30 seconds with liquid nitrogen (-170°C) applied with cotton-tipped applicators. BLI was acquired at 6 hours and 1, 3, and 7 days after treatments. RESULTS: In vitro, BLI signal showed a negative correlation with the number of freeze-thaw cycles (r = -0.86, P = .02). In vivo, there was no difference in tumor volume at 1 day after cryoablation among all groups, but the BLI signals were significantly different between G0 and G2/G3 (P = .03 and P = .02, respectively) and between G1 and G3 (P = .04). BLI signals reflected tumor growth speed and survival ratio. CONCLUSIONS: This study demonstrates the direct validation of BLI as a quantitative tool for the early assessment of therapeutic effects of cryoablation.

The Effect of Perinatal Gadolinium-Based Contrast Agents on Adult Mice Behavior.

OBJECTIVES: The aim of this study was to examine the effects of perinatal exposure to gadolinium (Gd)-based contrast agents (GBCAs) on the behavior of adulthood offspring. MATERIALS AND METHODS: Pregnant Balb/C mice (n = 5 per group) were intravenously injected with gadoterate meglumine (Magnescope, macrocyclic GBCA), gadodiamide (Omniscan, linear GBCA), or vehicle from pregnancy day 15 to 19, corresponding to embryonic day 15 to 19 of the fetus, at 2 mmol/kg body weight per day. Brain samples from dams and pups were collected on postpartum day 28. The total Gd concentration was quantified by inductively coupled plasma-mass spectrometry (dams, n = 3; gadoterate meglumine-treated pups group, n = 9; and gadodiamide-treated pups group, n = 10). Behavioral testing of offspring was started on postpartum day 70 (control group, n = 22; gadoterate meglumine-treated group, n = 23; and gadodiamide-treated group, n = 20). RESULTS: Higher levels of Gd retention were observed in dams and pups in the gadodiamide-treated group. Perinatal exposure to GBCAs caused anxiety-like behavior, disrupted motor coordination, impaired memory function, stimulated tactile sensitivity, and decreased muscle strength, particularly in the gadodiamide-treated group. CONCLUSIONS: In the present study, we showed that Gd was transferred to pups and was retained in their brain during postnatal development. Gadolinium retention may lead to impaired brain development. These findings indicate that the use of GBCAs in pregnant women should be avoided because it may have adverse effects on the fetus, particularly on brain development.

Organ retention of gadolinium in mother and pup mice: effect of pregnancy and type of gadolinium-based contrast agents.

PURPOSE: To investigate the effect of pregnancy and type of gadolinium (Gd)-based contrast agents (GBCAs) on organ retention of Gd in mother and pup mice after maternal administration. MATERIALS AND METHODS: Gd-DTPA-BMA (gadodiamide) or Gd-DOTA (gadoterate dimeglumine) was administered (2.0 mmol/kg of maternal weight) four times to pregnant Balb/c mice from gestational day 16-19, respectively. At 28 days after birth, they were euthanized and their organs (blood, brain, liver, kidney, spleen, and bone) were removed for the measurement of Gd by inductively coupled plasma mass spectrometry. RESULTS: Gd retention in maternal organs was generally lower than that in the organs of non-pregnant mice in both Gd-DTPA-BMA and Gd-DOTA groups. Significantly higher Gd retention was observed in the organs of pups whose mothers were administered Gd-DTPA-BMA as compared to those whose mothers were administered Gd-DOTA. Tissue-to-muscle ratio in the brains of pups was higher than that of mothers. CONCLUSION: We demonstrated in utero transplacental Gd retention in pups. In various organs in both mothers and pups, Gd retention was consistently higher for Gd-DTPA-BMA than Gd-DOTA administration. Pregnancy affected Gd retention in many maternal organs.