Kinetics and dosimetry of iodine-131-labelled antibody fragments after local administration in patients with rectal cancer

Abstract

In 11 patients with rectal cancer, a mixture of F(ab′)₂ fragments of anti-carcinoembryonic antigen and anti-CA 19.9 labelled with a diagnostic dose of iodine-131 (3–10 MBq) was administered submucosally around the tumour. In this study, the local kinetics in and the dose to the rectal wall, the whole body kinetics and the effective dose equivalent are presented. The early disappearance of the activity from the injection spot was characterized by a T _1/2 of 21 h. Initially, about 50% of the plasma activity was due to free ¹³¹I. After 4 h, the plasma activity was almost completely protein bound (86%). Maximum plasma activity was observed after the 2nd day. From 72 h p.i., the plasma activity decreased with a T _1/2 of 53 h. In the first 24 h, 14% of the injected dose was excreted in the urine and within 4 days about half of the administered activity. The absorbed radiation dose to the rectal wall was estimated to be 0.2 Gy/MBq, presuming a 20 cm³ distribution volume. The dose to the bone marrow was 0.2 mGy/MBq or 0.4 mGy/MBq, assuming a homogeneous tracer distribution or equal blood and bone marrow activity concentrations, respectively. The effective dose equivalent is 1.9 mSv/MBq, mainly determined by the dose to the rectal wall and to a lesser extent by the dose to the remaining body. Postulating comparable kinetics, ¹²³I- or ¹¹¹In- or ^99mTc-labelled fragments would result in 4-25-fold lower effective dose equivalents. We conclude that the theoretical advantages of the local administration of ¹³¹I-labelled antibodies for diagnostic purposes in patients with rectal cancer are not limited by our dosimetric data. Nevertheless, we advocate the use of other radiolabels with more appropriate imaging qualities and probably a lower radiation burden.