Imaging and staging of head and neck cancer using a low pH in-111-bleomycin complex

Bleomycin (BLM), a natural antibiotic toxic to dividing cells has been used for treatment of several forms of cancer. BLM has been labelled with various cations but most have turned out to be unstable in vivo. In-BLM has demonstrated high bone marrow uptake, but by using an In-111-bleomycin complex (BLMC) formed at low pH, the low in vivo stability and high bone marrow uptake can be avoided. Our premise is to combine radiotherapy and chemotherapy by using radionuclide-BLMC.

In this study we used In-111-A′2_a−c-BLMC in 28 head and neck cancer patients. Scintigraphic findings were compared to those of surgery, pre-operative radiology and proliferation markers. The injected patient activity was approximately 85 MBq, 100 MBq/mg.

The half-life of In-111 activity in serum varied from 1.5 to 3.1 h, and in urine from 1.4 to 3.7 h. More than 95% of the urine activity was excreted within 24 h. From biopsies obtained from surgical specimens of 22 patients the absolute uptakes in tumour tissues varied between 0.10 and 0.95 × 10⁻³% ID/g. Uptakes in normal tissues varied from 0.01 to 0.32 × 10⁻³% ID/g, and were always lower than in malignant tissues of the same patients. All patients were examined on the injection day with ultrasonography of the neck. Using In-111-BLMC we missed small metastatic lymph nodes (< 1 cm) in 2 patients, but there were no false positive findings. The critical organ from the dosimetric point of view was the kidney. The absorbed radiation doses with these injected activities were 19 mGy in liver, 75 mGy in kidney and 1.0 mGy in whole body (5 h mean residence time). Our results indicate that In-111-BLMC targets head and neck cancer, and identifies metastatic spread. It could possibly be applied with higher activities for adjuvant Auger-electron therapy of head and neck cancer.