title: Radiolabeled antibody combined with external radiotherapy for the treatment of head and neck cancer: reconstruction of a theoretical phantom of the larynx for radiation dose calculation to local tissues.
abstract: We propose to use radiolabeled antibodies in combination with external beam radiotherapy to improve locoregional control of head and neck cancer. In this case radiation toxicity to mucosa may become a dose-limiting factor and a calculation of the possible compensatory decrease to the external beam radiotherapy would be needed. For this purpose, the following theoretical phantom of a representative organ of this anatomic region, the larynx, was reconstructed and local dosimetric data were derived for a selection of beta-emitting isotopes. The phantom was reconstructed as cylindrical concentric tubes using the established values of an outer diameter of 38 mm and a height of 44 mm. Published mean adult larynx weight (28 g) and cartilage weight (14.7 g) were used. Mean mucosa weight from 5 mucosa samples of our patients was calculated to be 2.0 +/- 0.4 (SD) g. The remaining weight was apportioned to a fat/muscle compartment (11.3 g). The specific gravity of cartilage (1.10 g/cm3), mucosa (1.04 g/cm3), and fat/muscle (1.04 g/cm3) were used to cross-check the volume/mass disparity of the theoretical tubular tissue shells. The established maximum glottic diameter of 24 mm was used to calculate the central air column volume. Mean laryngeal tumor volume from 8 representative laryngeal tumors was 4.4 +/- 3.1 cm3. Tissue compartment thickness was 660 microns for mucosa, 3100 microns for muscle/fat, and 3320 microns for cartilage. These values allowed the calculation of dose absorbed fractions for a number of theoretical radioimmunoconjugates by extending the established calculation of absorbed fractions for spheres of known diameter to absorbed fractions of tissue planes (annuli) of known thickness. We calculated a Deq for the respective tissues in the larynx for 131I-, 186Re-, 188Re-, 67Cu-, 90Y-, and 153Sm-labeled HMFG1. Compensatory decrease to the external radiotherapy dose is 1.1 Gy for each injection of the radioimmunoconjugate we propose to use (131I-HMFG1). This would be best implemented through the modification of the external radiotherapy fractions falling within 2 effective half-lives of this radioconjugate in the mucosa.
authors.affiliation: Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Maraveyas
authors.forename: M
authors.initials: M
authors.lastname: Myers
authors.forename: N
authors.initials: N
authors.lastname: Stafford
authors.forename: G
authors.initials: G
authors.lastname: Rowlinson-Busza
authors.forename: J S
authors.initials: JS
authors.lastname: Stewart
authors.forename: A A
authors.initials: AA
authors.lastname: Epenetos
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007830:Larynx / Q000033:anatomy & histology* / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D008953:Models, Anatomic; D009092:Mucous Membrane / Q000033:anatomy & histology / Q000528:radiation effects; D011835:Radiation Protection; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes