(T1430-10-58) Tissue Distribution using Quantitative Whole Body Autoradiography (QWBA) of [¹⁴C]-Paclitaxel in Tumor Bearing Mice

Tuesday, October 18, 2022

2:30 PM – 3:30 PM ET

Presenting Author(s)

Leah R. Lake, MS (she/her/hers)

Group Leader of Autoradiography
WuXi AppTec
Cranbury, New Jersey, United States

Main Author(s)

MS

Megan E. Smith, MS

WuXi AppTec
Cranbury, New Jersey, United States

Purpose: Quantitative whole body autoradiography (QWBA) methodologies can be utilized not only to understand drug distribution in healthy tissues and tissue systems, but also in mutations that present as tumors as well as the vasculature that supplies these tumors. In this project, we evaluated the tumors derived from MBT2 and MC38 cell lines for colorectal and urinary bladder cancers, respectively, along with the corresponding tissue type for evaluation of differences between these types of tumor cells in female C3H/He and C57BL/6, respectively. Present tumors, vascularity, and corresponding tissues of interest were then analyzed to evaluate the differences in distribution of [¹⁴C]-Paclitaxel-derived radioactivity using QWBA methods.

Methods: Female C3H/He (n = 4) and C57BL/6 (n = 4) mice were inoculated with MBT2 and MC38 tumor cells, respectively, and the tumors were allowed to grow for twenty two days, when they measured an average volume of 404 mm³ and 183 mm³, respectively. The mice were then administered a single intravenous dose of [¹⁴C]-Paclitaxel (2.5 mg/kg, 146 µCi/kg) formulated in 10% Tween 80 and ethanol. At select time points following dose administration, one mouse per time point per strain was collected, frozen, and processed using QWBA cryo-sectioning and bio-imaging techniques. Images were then quantified for total radioactivity to evaluate distribution throughout the body and to the tumors.

Results: [¹⁴C]-Paclitaxel was widely distributed throughout the body, with the majority of tissues showing the highest concentrations at 0.5 or 1 hour post-dose in the female mice, and then quickly began to clear from the body. Vasculature to the MBT2 and MC38 tumors was identified, and the concentrations remained above the lower limit of quantification (LLOQ) at 24 h post-dose, while the concentrations in the blood throughout the body fell below the LLOQ by 24 h. Similarly, the concentrations observed in the tumors was lower than a majority of the tissues up to 24 h post-dose, thought the concentrations increased in the tumors over time. By 24 h post-dose, the concentrations in the tumors remained higher than the majority of tissues. This likely indicates that the Paclitaxel is continuing to target the tumor at later time points, while continuing to clear from the rest of the body.

Conclusion: We were able to confirm that we can successfully analyze the presence of radiolabeled [¹⁴C]-Paclitaxel-derived radioactivity not just throughout the body, but also within the tumors and vascular supply to the tumors using QWBA methodologies. QWBA is useful for a variety of oncological studies that involve drugs targeting the tumor itself, as well as anti-angiogenic drugs that target the vascular supply. QWBA’s unique ability to show specific regions of distribution allows scientists to distinguish exactly where the drug is present. This ability to detect the specific pathway of oncologic therapies can be useful in verifying if a drug is targeting tumors, their vascular supply, or tissues within the body.

Acknowledgments: Thank you to Moravek Biochemicals, Inc. for providing the isotope used in the experiment.

Concentrations of [14C]-Paclitaxel-Derived Radioactivity After a Single Intravenous 2.5 mg/kg Dose to Female C57BL/6 Mice

Representative Whole Body Autoradioluminogram Showing Tissue Distribution of [14C] Paclitaxel Derived Radioactivity at 1 Hour After an Intravenous Dose of [14C] Paclitaxel at 2.5 mg/kg to Female C3H/He Mice

Concentrations of Concentration of [14C]-Paclitaxel Derived Radioactivity (ng equiv/g) in Tissues of Female C57BL/6 Mice Following an Intravenous Dose of [14C]-Paclitaxel at 2.5 mg/kg (146 µCi/kg)

(T1430-10-58) Tissue Distribution using Quantitative Whole Body Autoradiography (QWBA) of [14C]-Paclitaxel in Tumor Bearing Mice

Presenting Author(s)

Main Author(s)

(T1430-10-58) Tissue Distribution using Quantitative Whole Body Autoradiography (QWBA) of [¹⁴C]-Paclitaxel in Tumor Bearing Mice