Fractionated 131I anti-CEA radioimmunotherapy: effects on xenograft tumour growth and haematological toxicity in mice

Abstract

Dose fractionation has been proposed as a method to improve the therapeutic ratio of radioimmunotherapy (RIT). This study compared a single administration of 7.4 MBq 131I-anti-CEA antibody given on day 1 with the same total activity given as fractionated treatment: 3.7 MBq (days 1 and 3), 2.4 MBq (days 1, 3, and 5) or 1.8 MBq (days 1, 3, 5, and 8). Studies in nude mice, bearing the human colorectal xenograft LS174T, showed that increasing the fractionation significantly reduced the efficacy of therapy. Fractionation was associated with a decrease in systemic toxicity as assessed by weight, but did not lead to any significant decrease in acute haematological toxicity. Similarly, no significant decrease in marrow toxicity, as assessed by colony-forming unit assays for granulocytes and macrophages (CFUgm), was seen. However, there was a significant depression of CFUgm counts when all treated animals were compared with untreated controls, suggesting that treatment did suppress marrow function. In conclusion, in this tumour model system, fractionated RIT causes less systemic toxicity, but is also less effective at treating tumours.

Figure 1

Distribution of ¹³¹I-labelled A5B7 at the 24 and 48 h time points (with associated standard deviations) in the tissues of mice bearing LS174T xenografts (n=4 at each time point).

Figure 2

Individual tumour growth assessed using serial three-dimensional measurements of tumour size to estimate tumour volume.

Figure 3

(i) The Kaplan–Meier plot showing the difference in survival of untreated and treated mice receiving 7.4 MBq of ¹³¹I-A5B7 administered as either a single therapy dose or multiple fractions. (ii) Mean survival times assessed by the log-rank method.

Figure 4

(i) Mean animal weights over time expressed as a percentage of baseline weight (±s.d.). (ii) Mean nadir weights as a percentage of baseline weight (±95% CI).

Figure 5

Blood indices as a percentage of baseline following therapy with associated standard deviations.

Figure 6

(i) Mean CFU_gm colony counts per 10⁵ mononuclear cells alongside those of age matched untreated controls +95% CI. (ii) Comparison between pooled CFU_gm colony counts per 10⁵ mononuclear cells for treated and untreated animals.