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Pharmacokinetics, Biodistribution, and Dosimetry of Specific and Control Radiolabeled Monoclonal Antibodies in Patients with Primary Head and Neck Squamous Cell Carcinoma

Department of Clinical Oncology [A.M., J.S. W.S., A.A.E.] and Tumour Targeting Laboratory [A.M., G.R-B., A.A.E.], ICRF Oncology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS, and Department of Ear, Nose and Throat Surgery, St. Mary's Hospital, Praed Street, London W2 1NY [N.S.], United Kingdom

The pharmacokinetics, biodistribution, and dosimetry of an IgG1 radiolabeled anti-mucin mAb (HMFG1) and an isotype-matched control (4D513) were studied in 29 patients with primary head and neck squamous cell carcinoma. Patients were given injections at 3 fixed time points prior to surgery, i.e., 24 (n = 12), 48 (n = 9), or 72 (n = 8) h. They were subsequently classified into two groups based on their immunohistochemical positivity for polymorphic epithelial mucin. Fourteen patients (48%) were positive, 5 of which were studied with both antibodies; and 15 patients were negative (52%), 7 of which were studied with both antibodies. There was no significant difference in serum pharmacokinetics and cumulative urinary clearance of the two antibodies. There was no significant difference in overall normal tissue uptake of specific and control antibody; however, when each component of the normal tissue category was analyzed individually, there was a significantly increased uptake of HMFG1 in mucosa as compared to control antibody. Immunohistochemical studies revealed positive staining of mucosa with HMFG1.

There was significantly increased uptake of specific antibody in antigen-positive tumors as compared to uptake of control antibody (P < 0.02). A tendency for less label loss over time from positive tumors as compared to control was documented. Absolute antibody uptake and tumor/normal tissue ratios demonstrated significant overlap in individual patients from each category depending on the specific ratio (e.g., tumor/adipose tissue) or time point studied; hence arbitrary cutoff values could not be recommended as indicators of specific uptake. Specificity and localization indices were the most reproducible indicators of specific localization.

Areas under the curve were calculated for all tissues, and local dosimetry for the two ß-emitting isotopes ¹³¹I and ⁹⁰Y is presented. The D_eq values for antigen-positive tumors were 2.9 cGy/mCi for ¹³¹I and 9.0 cGy/mCi injected for ⁹⁰Y. For antigen-negative tumors these values were significantly lower at 0.83 and 2.4 cGy/mCi of ¹³¹I and ⁹⁰Y, respectively. Bone marrow D_eq was calculated to be 0.87 cGy/mCi of ¹³¹I-HMFG1 injected.

Because the purpose of our ongoing research is to assess the therpauetic potential of the combination of radiolabeled antibody and external radiotherapy, detailed dose calculation to local dose-limiting tissues is required. D_eq to mucosa was calculated to be 1.1 and 3.8 cGy/mCi of injected ¹³¹I and ⁹⁰Y, respectively.

We conclude that a 9-10-Gy dose increment may be achieved in two administrations of 150 mCi of ¹³¹I-HMFG1 during a course of external radiotherapy. This may lead to improved control of local disease in patients with head and neck cancer.

¹ A. M. acknowledges the financial support of the A. G. Leventis Foundation. To whom requests for reprints should be addressed.

Received 7/11/94. Accepted 1/ 3/95.

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