Figure 4
Tissue biodistribution of 89Zr-oxine labeled huLym-1-A-BB3z-CAR T-cells dose escalation. Significant changes in %ID/g overtime were observed in all regions. (a–g) In vivo blood, bone, brain, liver, lungs, spleen, and tumor %ID/g of Raji-bearing NSG mice administered with low (mean ± SD: 126.7 ± 2.5 kBq, 1.87 ± 0.04 × 106 cells), middle (542,6 ± 92.1 kBq, 7.14 ± 0.45 × 106 cells) or high dose (1491.7 ± 36.1 kBq, 16.83 ± 0.41 × 106 cells) of 89Zr labeled huLym-1-A-BB3z-CAR T-cells (Low dose, n = 3 mice; Middle dose, n = 5 mice; High dose, n = 3 mice). Columns with error bars indicate means and standard deviations (SD) and open circles as individual data points. (h) Tumor-to-blood ratio obtained by dividing tumor %ID/g by blood %ID/g to account for cell signal accumulation in extravascular tumor tissue. Significant cell accumulation was observed by beginning on day 1 to day 5 in NSG mice that received the middle dose, and in mice that received low dose on day 2, by one-sample t-test vs. 0.6 threshold to overcome the enhanced permeability and retention (EPR) effect. (i) Ex vivo biodistribution %ID/g of low, middle, and high CAR T-cell doses on day 6 post CAR T-cell injection. Columns and error bars indicate means and SD, respectively. Statistically significant findings between comparisons are indicated with p-values above brackets. A value of p < 0.05 was used to indicate statistical significance.
