title: Higher dose and dose-rate in smaller tumors result in improved tumor control.
abstract: Small tumors are more sensitive to radioimmunotherapy (RIT) than larger ones. A greater proportion of viable radiosensitive areas in small tumors, higher antibody uptake, and radiation dose may be responsible. Six groups of mice with small (median tumor size 0.06 cm3) or large LoVo xenografts (median tumor size 0.38 cm3) received either RIT using a 131I-labeled anti-CEA antibody A5B7, 5-fluorouracil (5-FU) modulated with folinic acid (FA), or no treatment. The % injected activity/gram, antibody distribution in viable and necrotic areas, and dose distribution were determined. High-power microscopy images of the original section were reconstructed to estimate the proportion of viable areas. Mice with small and large tumors grew significantly less rapidly when treated with RIT compared to the control group (p < 0.0004 and p < 0.003, respectively), while 5-FU was ineffective. Small tumors treated with RIT grew less than large tumors (p < 0.02). A higher amount of % injected activity/gram of tumor (median 26.6% vs. 8.1%, p = 0.0007) and a higher dose-rate were found in small tumors at 24 hours post injection (viable areas: 56.2 +/- 23.7 vs. 13.3 +/- 7 cGy/h, necrosis 19.2 +/- 16.3 vs. 4.9 +/- 4.7 cGy/h, p = 0.0007). It appears that as viable tumor masses grow the access to them decreases and this has a fourfold effect on dose delivered for RIT in this example. These data support the consideration of use of RIT for adjuvant treatment in colon cancer.
authors.affiliation: Cancer Research UK Targeting and Imaging Group, Department of Oncology, Royal Free Campus, Royal Free and University College Medical School, University College London, London, UK. a.mayer@ucl.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Mayer
authors.forename: E
authors.initials: E
authors.lastname: Tsiompanou
authors.forename: A A
authors.initials: AA
authors.lastname: Flynn
authors.forename: R B
authors.initials: RB
authors.lastname: Pedley
authors.forename: J
authors.initials: J
authors.lastname: Dearling
authors.forename: R
authors.initials: R
authors.lastname: Boden
authors.forename: R H J
authors.initials: RH
authors.lastname: Begent
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D011879:Radiotherapy Dosage; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes