A novel technique, using radioluminography, for the measurement of uniformity of radiolabelled antibody distribution in a colorectal cancer xenograftmodel

Purpose: Radioimmunotherapy of cancer employs an antitumour antibody to car ry a radionuclide selectively to deposits of cancer. Conventional dose esti mates, based on the Medical Internal Radiation Dose (MIRD) formulation, ass ume uniform distribution of radiolabelled antitumour antibody within tissue source regions. This assumption has been tested by using a statistical mod el to predict the pixel value distribution obtained from the digitised radi oluminographs of a known radioactive source. The model uses the statistical nature of the detection of radiation where any uniform source distribution can be expected to have a detected histogram of pixel counts that is norma l or Gaussian. Therefore, any test for the degree of normality in the detec ted distribution is also a measure of the degree of uniformity in the sourc e. Methods and Materials: Three statistical techniques have been used to test the normality of the histogram of pixel values produced from the antibody d istribution in a tissue section. Kurtosis, skew, and Lilliefor's are tests for normality and have statistically defined critical values for a normal d istribution. After administration of I-125-labelled F(ab)(2) antibody to nu de mice bearing the LS174T colorectal cancer xenograft, the uniformity of a ntibody distribution in tumour and healthy tissues is measured using the ra dioluminographs of formalin-fixed paraffin sections. The test statistic for kurtosis, skew, and Lilliefor's is calculated for each tissue and is compa red to critical values from statistical tables. Results: The radiolabelled antibody is distributed uniformly in liver, sple en, muscle, lung, and colon and, therefore, conforms to conventional use of the MIRD formulation. The study showed that the kidney cortex and medulla should be considered separately in macroscopic absorbed-dose calculations, as should bone marrow and hard bone. Antibody heterogeneity in the tumour n ecessitates the incorporation of a microdosimetric tumour model into a macr odosimetry model for the accurate calculation of absorbed dose in all tissu es. (C) 1998 Elsevier Science Inc.