Summary Preliminary data from recent clinical radioimmunoscintigraphy studies indicate that 99mTc-labelled murine monoclonal antibodies (MAbs) E48 and U36 have a similar ability to target squamous cell carcinoma of the head and neck (HNSCC) selectively. In the present study we describe additional aspects of murine and chimeric MAb (mMAb and cMAb) E48 and U36, which might influence the selection of one MAb for adjuvant radioimmunotherapy. To make direct comparison possible, ten patients received 11.2 ± 0.3 and 11.1 ± 0.2 mg (n = 5) or 51.1 ± 0.1 and 51.0 ± 0.4 mg (n= 5) of both mE48 IgG and mU36 IgG labelled with 1311 and 1251 simultaneously and underwent surgery 7-8 days after injection. The mean uptake of iodine-labelled mE48 IgG and mU36 was highest in tumour tissue, 8.9 ± 8.9 and 8.2 ± 4.4 %ID kg-' respectively. Tumour to non-tumour ratios for oral mucosa, skin, muscle, blood and bone marrow aspirate were 2.5, 5.5, 25.2, 4.7 and 4.0 respectively in the case of mE48 IgG and 2.3, 4.1, 21.0, 5.8 and 5.8 respectively in the case of mU36 IgG. The distribution of mMAbs E48 and U36 throughout tumours that had been collected in previous studies was heterogeneous when administered at a dose of 1 or 12 mg, and homogeneous when administered at a dose of 52 mg. Administration of mE48 IgG (1-52 mg) resulted in a human anti-mouse antibody response in 12 out of 28 patients, while for mU36 IgG (1-52 mg), this figure was three out of 18 patients. cMAb E48 was shown to be highly effective in mediating antibody-dependent cellular cytotoxicity in vitro, while cMAb U36 and mMAbs E48 and U36 were not effective at all. Rationales are provided that give priority to the start of adjuvant radioimmunotherapy trials with 1'6Re-labelled cMAb U36 IgG in head and neck cancer patients who are at high risk for the development of locoregional recurrences and distant metastases.Keywords: monoclonal antibodies; head and neck cancer; squamous cell carcinoma; biodistribution; human anti-mouse antibody response; antibody-dependent cellular cytotoxicityDuring 1996 approximately 41 090 Americans will develop head and neck cancer and 12 510 will die from it. Worldwide more than 500 000 new cases are projected annually, and the incidence is rising. In head and neck cancer, squamous cell carcinoma accounts for approximately 90% of all tumours (Parker et al, 1996). About one-third of these patients present with early-stage (I and II) head and neck squamous cell carcinoma (HNSCC), while two-thirds present with advanced disease (stage III and IV) (Vernham and Crowther, 1994). Although early-stage HNSCC can, in the great majority of cases, be cured with surgery or radiotherapy alone, the local failure rate after surgery and/or radiotherapy in advanced stages is more than 50%. Moreover, about 25% of these patients develop distant metastases (Stupp et al, 1994).Despite an increase in the locoregional control of HNSCC, owing to improved surgery and radiotherapy, current therapy regimens have failed to increase the 5-year survival rate in HNSCC patients (Pa...

Summary Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 ± 1.39 jsCi ml-', indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 ± 0.03 cGy mCi-'. Red marrow dose was estimated to be between 0.18 ± 0.02 and 0.97 ± 0.12 cGy mCin'. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia.

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Twenty colorectal cancer patients were given an intravenous injection of human IgM monoclonal antibody (MAb) 16.88 (8 mg) conjugated to 131I for tumor localization. After a 2-week interval, a second injection with 200, 500, or 1000 mg of unlabeled antibody added was given to groups of five patients each. at the end of the 2-hour infusion, 66% of the radioactivity remained in the circulation. Blood clearance of the 131I-labeled MAb 16.88 was biphasic with a mean half-life (T1/2 alpha) of 12 hours and T1/2 beta of 45 hours. Clearance rate was 0.09 L/hour. More than 90% of the 131I in serum was protein bound, with an immunoreactive fraction of 80% in the first 48 hours. Size exclusion chromatography indicated no degradation products other than 131I in serum and urine. The urinary excretion rate of 131I increased to 1.5% of the dose per hour at 24 hours, with 50% of the dose excreted in 34 hours. The pharmacokinetic profile of 131I-labeled MAb 16.88 was neither influenced by the total protein dose of antibody administered nor affected by specific uptake in tumor tissue in individual patients, as determined on early immunoscintigrams. The larger antibody doses showed a slightly slower excretion of 131I. The assays applied to determine immunogenicity were enzyme-linked immunosorbent assay, radioimmunoassay, and the dot-blot assay. They had sensitivities ranging from 5 ng/mL to 0.5 micrograms/mL for goat or rabbit antihuman IgM. The assays did not reveal antihuman antibody responses.

SummaryBACKGROUND Justification for adjuvant radio-iodine (I-131) therapy in differentiated thyroid cancer (DTC) is purely based on retrospective data. This is true for ablative therapy and even more so for high-dosage adjuvant schedules. Randomized trials on the latter application are considered impossible due to anticipated formidable sample sizes required in a disease with an overall excellent prognosis like DTC.