Early detection of progressive disease using thyroglobulin doubling-time in metastatic differentiated thyroid carcinoma treated with radioactive iodine.

OBJECTIVE: Detectable serum thyroglobulin (Tg) in patients with differentiated thyroid carcinoma (DTC) after total thyroidectomy indicates progression of the disease. Thyroglobulin doubling-time (TgDT) is a powerful prognostic predictor in patients with DTC. We aimed to evaluate the value of the dynamic TgDT for early detection of progressive disease (PD) in the patients of metastatic DTC with I radioactive iodine (RAI) therapy. METHODS: We retrospectively evaluated 21 patients undergoing RAI therapy with metastatic DTC. Patients were defined as PD or non-PD according to Response Evaluation Criteria in Solid Tumors 1.1. TgDT was calculated by Excel-based software using Tg values measured during routine follow-up. Whole data (WDT), initial four data (IDT) and recent four data (RDT) of TgDT after total thyroidectomy were calculated and compared. RESULTS: Among the 21 patients (10 men; median age, 62 years old; range, 33-80), 11 patients were classified into PD and 10 were into non-PD. The initial Tg after total thyroidectomy showed a significant difference between PD and non-PD patients (P = 0.013). Short WDT, IDT and RDT (less than one year) showed a high correlation with PD (P < 0.05). RDT showed the highest predictive value for PD (P < 0.001). All the 11 PD patients showed RDT less than one year before PD (median follow-up, 157 days; range, 88-252). CONCLUSIONS: RDT is a powerful PD predictor in patients with metastatic DTC. Dynamic monitoring of RDT should be applied for the early detection of PD in clinic.

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.

Activatable fluorescence detection of epidermal growth factor receptor positive mediastinal lymph nodes in murine lung cancer model.

It is important to detect mediastinal lymph node metastases in patients with lung cancer to improve outcomes, and it is possible that activatable fluorescence imaging with indocyanine green (ICG) can help visualize metastatic lymph nodes. Therefore, we investigated the feasibility of applying this method to mediastinal lymph node metastases in an epidermal growth factor receptor (EGFR)-positive squamous cell carcinoma of the lung. Tumors were formed by injecting H226 (EGFR-positive) and H520 (EGFR-negative) cell lines directly in the lung parenchyma of five mice each. When computed tomography revealed tumors exceeding 8 mm at their longest or atelectasis that occupied more than half of lateral lung fields, a panitumumab (Pan)-ICG conjugate was injected in the tail vein (50 µg/100 µL). The mice were then sacrificed 48 hours after injection and their chests were opened for fluorescent imaging acquisition. Lymph node metastases with the five highest fluorescent signal intensities per mouse were chosen for statistical analysis of the average signal ratios against the liver. Regarding the quenching capacity, the Pan-ICG conjugate had almost no fluorescence in phosphate-buffered saline, but there was an approximate 61.8-fold increase in vitro after treatment with 1% sodium dodecyl sulfate. Both the fluorescent microscopy and the flow cytometry showed specific binding between the conjugate and H226, but almost no specific binding with H520. The EGFR-positive mediastinal lymph node metastases showed significantly higher average fluorescence signal ratios than the EGFR-negative ones (n = 25 per group) 48 hours after conjugate administration (70.1% ± 4.5% vs. 13.3% ± 1.8%; p < 0.05). Thus, activatable fluorescence imaging using the Pan-ICG conjugate detected EGFR-positive mediastinal lymph node metastases with high specificity.

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.