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A Transfectant Mosaic Xenograft Model for Evaluation of Targeted Radiotherapy in Combination with Gene Therapy In Vivo

¹ Targeted Therapy Group, Division of Cancer Science and Molecular Pathology, Glasgow University, Cancer Research United Kingdom Beatson Laboratories, Glasgow, United Kingdom; ² Department of Child Health, Yorkhill Hospital, Glasgow, United Kingdom; and ³ Targeted Therapy Group, Centre for Oncology and Applied Pharmacology, Glasgow University, Cancer Research United Kingdom Beatson Laboratories, Glasgow, United Kingdom

View larger version (15K): [in this window] [in a new window]   FIGURE 1.  131I-MIBG uptake by UVW and EJ138 cells—untransfected or transfected with the NAT gene controlled by the CMV, hTR, or hTERT promoter. Evaluation of uptake was performed in the presence or absence of DMI, a specific inhibitor of NAT-mediated uptake. Results are mean ± SD of 3 determinations performed in triplicate.

View larger version (19K): [in this window] [in a new window]   FIGURE 2.  Effect of 131I-MIBG (12 MBq) treatment of xenografts composed of UVW cells (A) or EJ138 cells (B). Cells were untransfected (parental) or transfected with the NAT gene under control of the strong ubiquitous viral promoter (CMV) or either of the human telomerase (hTR and hTERT) promoters. Each treatment group consisted of 12 mice. Results are mean ± SD.

View larger version (10K): [in this window] [in a new window]   FIGURE 3.  Relationship between production of NAT messenger RNA and percentage of NAT gene transfectants in TMXs derived from UVW or EJ138 cells. Results are mean ± SD of 6 determinations. Significant correlations were established in UVW xenografts (rs = 0.910; P < 0.001) and EJ138 xenografts (rs = 0.971; P < 0.001).

View larger version (9K): [in this window] [in a new window]   FIGURE 4.  131I-MIBG uptake by TMXs, derived from UVW or EJ138 cells, as a function of proportional content of NAT gene transfectants. Results are mean ± SD of 6 determinations. Significant correlations were established in UVW xenografts (rs = 0.966; P < 0.001) and EJ138 xenografts (rs = 0.970; P < 0.001).

View larger version (16K): [in this window] [in a new window]   FIGURE 5.  Effect of 131I-MIBG (12 MBq) treatment of TMXs composed of various proportions of UVW cells (A) or EJ138 cells (B). Cells were untransfected (0%) or transfected with the NAT gene under control of the hTR promoter. Each treatment group consisted of 12 mice. Results are mean ± SD.