So far, mAb E48 is the most promising antibody described for specific targeting of
head and neck squamous cell carcinoma (
HNSCC) in patients. On the basis of its more homogeneous reactivity pattern on
HNSCC, the novel mAb U36 may be even better suited for targeting. In this study the biodistribution of mAb U36 was evaluated by radioimmunoscintigraphy (RIS) and biopsy measurements in 10 patients who were suspected of having neck
lymph node metastases from a histologically proven
HNSCC and who had been scheduled to undergo resection of the primary
tumor and
neck dissection. Patients received 1.8-53.0 mg mAb U36
IgG labeled with 756 +/- 95 MBq technetium-99m i.v. Preoperatively, palpation, computerized tomography, magnetic resonance imaging, and RIS were performed. RIS images included planar and single-photon emission computerized tomography images of the head and neck and planar images of the whole body. The diagnostic findings were recorded per side as well as per lymph node level of the neck and compared to the histopathological outcome. Radioactivity in blood samples and biopsies from the surgical specimens were measured. All 10 primary
tumors were visualized by RIS. All diagnostic modalities were correct in 7 of 14
tumor-involved lymph node levels. The missed
lymph node metastases comprised
micrometastases, small
tumor-involved nodes (<9 mm), and
tumor-involved nodes with much
necrosis,
keratin, or
fibrin. There were no false-positive observations with mAb U36. Besides activity uptake in
tumor tissue, only a slight accumulation of activity was observed in the mouth, lungs, liver, spleen, kidneys, and scrotal area. Biopsies from the surgical specimen showed a high
tumor uptake of 20.4 +/- 12.4% of the injected dose/kg (range, 8.0-43.0% of injected dose/kg), 44 h postinjection. An increase in the mAb dose did not influence uptake of activity in
tumor tissue. The mean
tumor:nontumor ratio at this time point was 2.3 for mucosa, 2.8 for blood, 3.0 for bone marrow aspirate, 12.9 for fat, and 13.0 for muscle tissue. The present clinical study shows that technetium-99m-labeled U36
IgG accumulates selectively and to a high level in
HNSCC. The
tumor-targeting results for U36
IgG are comparable to those previously described for E48
IgG. On the basis of the results of ongoing biodistribution studies in which both mAbs E48 and U36, labeled with different
iodine isotopes, are simultaneously evaluated for
tumor uptake and retention in
HNSCC patients, one of these mAbs will be selected for future adjuvant
radioimmunotherapy trials.