Therapeutic Efficacy and Tumor Dose Estimations in Radioimmunotherapy of Intraperitoneally Growing OVCAR-3 Cells in Nude Mice with 211At-Labeled Monoclonal Antibody MX35 | Journal of Nuclear Medicine

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FIGURE 1.
Schematic illustration of dynamic compartment model and cumulated activity [Bq × s] curves for 1 tumor cell. (A and B) Compartments A and B represent the number of mAbs in the abdominal cavity and the number of mAbs bound to the cell surface of 1 tumor cell, respectively. N_mAb is the total number of mAbs injected intraperitoneally at t = 0 in 0.7 mL PBS. A_sp is the fraction of mAbs carrying an ²¹¹At atom. The k_on expresses the rate at which mAbs will bind to antigenic sites for a specific antigen concentration. It is assumed in the model that the mAbs are immediately and homogeneously mixed in the abdominal cavity after injection. (C) Illustration of how the reaction rate is affected by the number of mAbs injected by plotting the number of ²¹¹At-mAbs (N_At-mAb) bound to the cell surface as a function of time in the case of 1,200 (curve 1), 800 (curve 2), and 400 (curve 3) kBq of ²¹¹At-MX35 injected. (D–F) Curve 2 shows the cumulated activity on 1 tumor cell surface as a function of time after injecting 400 kBq of ²¹¹At-MX35. Curves 1 and 3 show the effect on the cumulated activity for a change of +50% and −50%, respectively, in the in vitro determined parameters A_sp, k_on, and B_max, a situation not unlikely to occur in an in vivo situation.
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FIGURE 2.
The absorbed dose at different distances from the center of the differently sized tumor cell clusters (r_cluster = 25 [A, D, and G], 50 [B, E, and H], and 100 [C, F, and I] μm) illustrated for the 3 different activity levels used (1,200 [A–C], 800 [D–F], and 400 [G–I] kBq) for 3 cases: ²¹¹At-MX35 homogeneously distributed over all cell surfaces throughout the whole cell cluster (•), ²¹¹At-MX35 homogeneously distributed only on the cell surfaces defining the surface of the cell cluster (▪), and ²¹¹At-MX35 homogeneously distributed in the abdominal fluid (no specific binding to the tumor cells at all) (▴).

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TABLE 1

Study Groups and Number of Mice with Macroscopic and Microscopic Tumors and Ascites

Group	n	Treatment	Activity (kBq)	Macroscopic tumor	Microscopic tumor	Ascites	TFF* (%)
1	9	PBS	—	6/9	9/9	9/9	0
2	9	MX35 in PBS	—	6/9	9/9	9/9	0
3	10	²¹¹At-MOv18 in PBS	377–419	0/10	3/10	0/10	70
4	10	²¹¹At-MX35 in PBS	389–422	0/10	2/10	1/10	80
5	10	²¹¹At-MX35 in PBS	774–808	0/10	4/10	2/10	50
6	5	²¹¹At-MX35 in PBS	1,167–1,211	0/5	2/5	0/5	60

↵* TFF = tumor-free fraction (i.e., no macroscopic and microscopic tumors and no ascites).
The presence of macroscopic tumors and ascites was assessed by careful ocular inspection during dissection 2 mo after administration of the different regimes. Microscopic tumor growth was assessed by histopathologic methods using paraffin-embedded biopsies stained with eosin–hematoxylin and microscopy at 40× magnification.