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Reduced Myelotoxicity with Sustained Tumor Concentration of Radioimmunoconjugates in Rats after Extracorporeal Depletion

Linda Mårtensson1, Rune Nilsson2, Tomas Ohlsson3, Hans-Olov Sjögren4, Sven-Erik Strand3 and Jan Tennvall1

1 Department of Oncology, Lund University, Lund, Sweden; 2 Mitra Medical AB, Lund, Sweden; 3 Department of Medical Radiation Physics, Lund University, Lund, Sweden; and 4 Department of Immunology, Lund University, Lund, Sweden


Figure 1
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  		FIGURE 1.  Experimental ECAT setup. Cannula is inserted into one of lateral tail veins (1) for return of blood and is connected to extracorporeal system (regulated by the pump (2)). For blood access, another cannula is inserted into ventral tail artery (3). When cannulas are inserted, extracorporeal circulation is begun in bypass mode (4) without column connected. Once the circuit is filled with blood and any air bubbles in circuit have been collected in the air trap (5), column (6) is connected to the circuit and affinity adsorption is begun.

 

Figure 2
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  		FIGURE 2.  WBC (A), PLT (B), and RBC (C) as function of time after injection (p.i.) when rats were injected with 800 MBq/kg 177Lu-conjugated, biotinylated BR96 and subjected to ECAT 12 h after injection ({circ}), 24 h after injection ({blacksquare}), and 48 h after injection ({square}). Results from control animals (not subjected to ECAT) are also plotted (•).

 

Figure 3
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  		FIGURE 3.  WBC (A), PLT (B), and RBC (C) as function of time after injection (p.i.) when rats were injected with 400 MBq/kg 90Y-conjugated, biotinylated BR96 and subjected to ECAT 12 h after injection ({circ}), 24 h after injection ({blacksquare}), and 48 h after injection ({square}). Results from control animals (not subjected to ECAT) are also plotted (•).

 

Figure 4
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  		FIGURE 4.  Scintillation camera images (A) of tumor in 1 animal in each group (12, 24, and 48 h after injection) before ECAT (top row) and after ECAT (bottom row) showing that activity in surrounding tissues is efficiently eliminated by ECAT, whereas activity in tumors is sustained. Reduction in activity in tumors is shown for groups (n = 6) subjected to ECAT 12, 24, and 48 h after injection of RIC (B).

 

Figure 5
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  		FIGURE 5.  AUC for blood (hatched area) and tumor activity is plotted for control animals not subjected to ECAT (A), ECAT simulated at 12 h after injection (B), at 24 h after injection (C), and at 48 h after injection (D) for animals injected with 177Lu-conjugated, biotinylated BR96. %ID/g = percentage injected dose per gram.

 




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