Comparison of systemic radiotherapy with I-131-labeled monoclonal antibody BW575/9 to external beam radiotherapy in human neuroblastoma xenografts.
The therapeutic effectiveness of external beam radiotherapy (XRT) and radioimmunotherapy (RIT) was investigated in a human neuroblastoma (SK-N-SH) xenotransplanted to nude mice. This tumor model seems especially suitable for comparison of the relative biological effectiveness of RIT vs. XRT, as--in contrast to most tumor models--it shows an unusually homogenous uptake of the labeled MAb, thus providing a homogenous intratumoral dose distribution. XRT was performed using single fractions of 800, 1600, 2000 and 2400 cGy and RIT was delivered by intravenous injection of 15, 19 and 26 MBq of the I-131-labeled monoclonal antibody (MAb) BW575/9. Therapeutic efficiency of the two radiation modalities was assessed in terms of tumor volume doubling time (VDT). Miniature thermoluminescent (mini-TLD) dosimetry and MIRD-based dose calculations were used to evaluate the absorbed doses delivered by RIT and to assess the degree of homogeneity of the dose distribution. RIT with 19 MBq of the I-131 BW575/9 delivered a tumor dose of 2820 cGy measured by TLD and resulted in a tumor VDT of 32 days (vs. one day in controls). An equivalent effect on VDT was achieved by a single fraction XRT of 1600 cGy. The relative efficiency of XRT compared with RIT (ratio of dose XRT/dose RIT required to give the same VDT) was 0.57. Application of 26 MBq of the MAb (= 3200 cGy) resulted in complete tumor regression after ten days as did XRT with 2400 cGy, corresponding to a relative efficiency of 0.75.
Sautter-Bihl
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ML
Klinik für Strahlentherapie und Nuklearmedizin, Städtisches Klinikum Karlsruhe.
Wessely
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Bihl
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology*; D005069:Evaluation Studies as Topic; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000532:radiotherapy*; D010315:Particle Accelerators; D016499:Radioimmunotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D011882:Radiotherapy, High-Energy / Q000379:methods*; D012062:Relative Biological Effectiveness; D013819:Thermoluminescent Dosimetry; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D007457:Iodine Radioisotopes