Filtration of a solution may lower metal concentrations through adsorption of metal species to the filter. Processes such as filter-sterilizing nutrient solution and filtration of field water are sensitive to these sorption artifacts, yet basic data on the affinity of different filters for metals are lacking. This article describes the adsorption of five metals to eight types of 0.2-microm membrane filters used for sterilizing a plant (Lemna minor L.) culture medium. Filters of cellulose acetate, cellulose nitrate, mixed cellulose ester, nylon, polyamide, polycarbonate, polyester, and polyvinylidene fluoride were tested for their affinity toward mono- (K), di-(Mn, Cu, Zn), and trivalent (lanthanum [La]) metals. Metal concentrations were quantified using radioisotopes and speciation was calculated. Results showed that metals had the lowest affinity for polycarbonate and nylon filters and the highest affinity for cellulose- and polyester-type filters. Furthermore, it was shown that the metal load on cellulose filters correlated best with free ion concentrations (indicating electrostatic attraction), while loads on other filters correlated better with total metal concentrations. Filtering a 5-ml solution of pH 5 did not affect its metal concentrations, ranging from 10 nM (La) to 49 microM (K). To minimize filtration artifacts, we propose using polycarbonate or nylon filters, especially when dealing with low volumes of high pH and low metal species concentrations.
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...
mAb hCTM01 binds a carcinoma-associated antigen, the MUC1 gene product. The antigen is also present in the circulation, and administration of 111In-labelled hCTM01 results in the formation of immune complexes with enhanced accumulation in the liver. To avoid the unwanted effect of circulating radioactive immune complexes, a strategy to remove the circulating antigen was investigated using a split-dosage schedule. Eleven patients suspected of having ovarian carcinoma were injected with 1 mg/kg unlabelled hCTM01, 1 h before receiving 0.1 mg/kg 111In-labelled hCTM01 (100 M Bq). The amount of radioactivity was determined in resected tumour tissue, various normal tissues and blood samples obtained at laparotomy 6 days postinjection (p.i.). In all patients, the circulating antigen decreased to its nadir after the unlabelled antibody infusion and immune complex formation was demonstrated. Uptake in tumour deposits 6 days p.i. was 11.1 times higher than in normal tissues (P < 0.0001) and 5.9 times higher than in blood (P < 0.0001). 111In activity in liver tissue was comparable to 111In uptake in tumour tissue, and considerably lower than previously reported in patients not pretreated with unlabelled antibody. The split-dosing strategy would appear to be advantageous for use of hCTM01 as a specific carrier for the delivery of cytotoxic agents to patients with ovarian cancer.
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