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Enhanced Efficacy of 90Y-Radiolabeled Anti-Lewis Y Humanized Monoclonal Antibody hu3S193 and Paclitaxel Combined-Modality Radioimmunotherapy in a Breast Cancer Model

Marcus P. Kelly, Fook T. Lee, Fiona E. Smyth, Martin W. Brechbiel and Andrew M. Scott
Journal of Nuclear Medicine April 2006, 47 (4) 716-725;

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Biodistribution of 90Y-hu3S193 in normal murine tissues, blood, MCF-7 tumors, and control SW1222 tumors at selected time points after injection into BALB/c nude mice. Results (%ID/g) are expressed as mean ± SD (n = 4–5).

  • FIGURE 2. 
    FIGURE 2. 

    Biodistribution of 90Y-hu3S193 in blood (▪), MCF-7 tumors (▴), and control SW1222 tumors (▾), with %ID/g expressed as mean ± SD (n = 4–5).

  • FIGURE 3. 
    FIGURE 3. 

    Uptake of 90Y-hu3S193 in tumor xenografts. Analysis of MCF-7 xenograft at 72 h after injection by hematoxylin–eosin staining (A), autoradiography (C), Ley immunohistochemistry (E), and huA33 immunohistochemistry (G). SW1222 control tumor xenograft at 72 h after injection by hematoxylin–eosin staining (B), autoradiography (D), Ley immunohistochemistry (F), and huA33 immunohistochemistry (H). V = viable tumor; N = necrotic.

  • FIGURE 4. 
    FIGURE 4. 

    MCF-7 xenograft growth (mm3) in response to single-dose treatment on day 0 with 90Y-hu3S193 (A) or isotype control 90Y-huA33 (B). Results are expressed as mean ± SD (n = 4–5).

  • FIGURE 5. 
    FIGURE 5. 

    MCF-7 xenograft curves after CMRIT in mice receiving PBS control (▪), 600 μg paclitaxel (▴), 90Y-hu3S193 and 600 μg paclitaxel (▾), 90Y-huA33 and 600 μg paclitaxel (⧫), and 90Y-hu3S193 (•) at doses of 0.46 MBq (A), 0.92 MBq (B), and 1.85 MBq (C) of 90Y-hu3S193 or 90Y-huA33. (D) MCF-7 xenograft growth after single treatments on day 0 of PBS control (□), 75 μg hu3S193 (▵), and 75 μg hu3S193 and 600 μg paclitaxel (▿). Results are expressed as mean ± SD (n = 4–5).

Tables

  • TABLE 1

    TV and Percentage Change in TV on Day 45 of Study

    TreatmentnTV (mm3) on day 0 of study (mean ± SD)TV (mm3) on day 45 of study (mean ± SD)Change in TV (%) on day 45 (mean ± SD)Response rate (%)
    PBS control4121.35 ± 43.091,069.52 ± 249.561,000.70 ± 537.930
     90Y-hu3S193 (0.46 MBq)5135.40 ± 27.86750.04 ± 236.12443.69 ± 79.520
     90Y-hu3S193 (0.92 MBq)5136.60 ± 25.35513.51 ± 226.64 (P = 0.01)*293.14 ± 212.24 (P = 0.0295)†0
     90Y-hu3S193 (1.85 MBq)3142.00 ± 27.2606.00 ± 10.39 (P = 0.0008)*−96.18 ± 6.62 (P = 0.0065)†33 PR/66 CR
     90Y-hu3S193 (3.70 MBq)5157.60 ± 37.0800.00 ± 00.00 (P < 0.0001)*−100.00 ± 00.00 (P = 0.0023)†100 CR
     90Y-huA33 (0.46 MBq)4147.00 ± 36.011,139.93 ± 127.10712.53 ± 233.940
     90Y-huA33 (0.92 MBq)3120.50 ± 54.84959.56 ± 157.81695.67 ± 595.060
     90Y-huA33 (1.85 MBq)4158.00 ± 44.68791.72 ± 300.34390.34 ± 55.190
     90Y-huA33 (3.70 MBq)2137.00 ± 25.43612.14 ± 32.25336.47 ± 101.210
    TXL (600 μg)5152.00 ± 33.79852.75 ± 353.44458.15 ± 178.420
     90Y-hu3S193 (0.46 MBq + TXL)5127.60 ± 32.79144.55 ± 107.91 (P = 0.0001)*16.99 ± 82.25 (P = 0.0046)†20 PR
     90Y-hu3S193 (0.92 MBq + TXL)5148.20 ± 24.08110.95 ± 94.24 (P < 0.0001)*−28.79 ± 51.04 (P = 0.0034)†40 PR
     90Y-hu3S193 (1.85 MBq + TXL)5161.00 ± 35.0800.00 ± 00.00 (P < 0.0001)*−100.00 ± 00.00 (P = 0.0023)†100 CR
     90Y-huA33 (0.46 MBq + TXL)4135.75 ± 39.68660.46 ± 270.02379.47 ± 85.090
     90Y-huA33 (0.92 MBq + TXL)3140.50 ± 25.68237.79 ± 86.22 (P = 0.0029)*58.98 ± 56.92 (P = 0.0320)†0
     90Y-huA33 (1.85 MBq + TXL)4123.25 ± 24.10198.92 ± 28.78 (P = 0.0004)*63.87 ± 22.74 (P = 0.0131)†0

    • ↵* Results of significant t test comparing mean TV of placebo PBS control group with all other treatments.

    • ↵† Results of significant t test comparing mean % change in TV from day 0 of placebo PBS control group with all other treatments.

    • n = number of mice; TXL = paclitaxel.

  • TABLE 2

    Comparison of Percentage Change in TV Between 90Y-hu3S193 and 90Y-huA33 Antibodies on Day 45

    TreatmentComparisonChange (%) in TV on day 45 (mean ± SD)P
    0.46 MBq90Y-hu3S193 vs. 90Y-huA33443.69 ± 79.52 vs. 712.53 ± 233.940.0450*
    0.92 MBq90Y-hu3S193 vs. 90Y-huA33293.14 ± 212.24 vs. 695.67 ± 595.060.0121*
    1.85 MBq90Y-hu3S193 vs. 90Y-huA33−96.18 ± 6.62 vs. 390.34 ± 55.19<0.0001*
    3.7 MBq90Y-hu3S193 vs. 90Y-huA33−100.00 ± 00.00 vs. 336.47 ± 101.21<0.0001*
    0.46 MBq + paclitaxel90Y-hu3S193 vs. 90Y-huA3316.99 ± 82.25 vs. 379.47 ± 85.090.0003*
    0.92 MBq + paclitaxel90Y-hu3S193 vs. 90Y-huA33−28.79 ± 51.04 vs. 58.98 ± 56.92NS
    1.85 MBq + paclitaxel90Y-hu3S193 vs. 90Y-huA33−100.00 ± 00.00 vs. 63.87 ± 22.74<0.0001*

    • ↵* Results of significant t test comparing equivalent doses of radiolabeled hu3S193 and huA33 antibody efficacy.

    • NS = not significant.

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