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Biomedical subjects

G L Denardo

Publications and source records attributed to G L Denardo.

8 recordsLinked to original sources
PubMed1995

Radioimmunotherapy of lymphoma: a UC Davis experience.

B-cell malignancies, such as malignant lymphoma and chronic lymphocytic leukemia, commonly present with advanced disease and multiple sites of involvement. Consequently, systemic combination chemotherapy is the standard therapeutic approach and cures about one half of these patients. Development of novel therapies is required if the remaining patients are to be cured of their malignancy. Lym-1, a mouse monoclonal antibody that is reactive with these malignancies, has been coupled with 131I or 67Cu and used to treat 55 patients with advanced B-cell malignancies that had proven resistant to standard therapy. The majority of the patients responded to this therapy and the survival of responders was longer than that of non-responders. Similar results have recently been reported by others. These results represent a remarkable achievement for single agent therapy because these trials were exploratory in nature and most of the patients had failed many chemotherapy regimens. The toxicities were in general mild and readily manageable. It appears that enhancing strategies are likely to improve upon these results by increasing the therapeutic index.

Animals↗
PubMed1989

Effect of different linkages between chelates and monoclonal antibodies on levels of radioactivity in the liver.

After injection of radiometal labeled antibodies, the radionuclide accumulates in the liver. This might be altered by a metabolizable linkage between metal chelate and antibody. Four benzyl-EDTA chelating agents were synthesized and conjugated to mouse monoclonal antibody Lym-1. Liver uptake of 111In in nontumored mice 72 h after injection was 2.2, 13.4, 7.6 and 20% for disulfide, thioether, thiourea or peptide linkages, respectively. 111In excreted in the urine was still in the benzyl-EDTA chelate form, as shown by binding to a specific anti-chelate antibody.

Animals↗
PubMed1988

Uptake of indium-111-labeled monoclonal antibody ZME-018 as a function of tumor size in a patient with melanoma.

The accumulation of an Indium-111-labeled monoclonal antibody (MoAb), ZME-018, in melanoma tumors in a patient was determined by sequential, quantitative gamma camera imaging. The amount and concentration of In-111 in each tumor changed in a characteristic pattern with time, reaching a peak at day 3 followed by a steady clearance. The concentration of In-111 in the tumor and the ratios of tumor to whole-body or blood decreased as the size of the tumor increased. These results were interpreted to indicate that the fraction of active, perfused tumor decreased as the melanoma lesions increased in size. The maximum number of MoAb molecules bound per melanoma cell was calculated to be abut 35,000. The implications of these observations for radioimmunoimaging and therapy are significant.

Antibodies, Monoclonal↗
PubMed1986

123I radiolabeling of monoclonal antibodies for in vivo procedures.

When labeled to monoclonal antibodies (MAbs) or their fragments, 123I can be used for imaging or for predicting the treatment potential and radiation dosimetry of 131I labeled to the same molecular species. Because 123I (p,5n) from the Crocker Nuclear Laboratory is in dilute solution, when compared with commercial 125I of labeling grade, we have evaluated labeling parameters using Chloramine-T as the oxidant and derived an optimum set of labeling conditions that provide a 60-80% radiochemical yield of highly immunoreactive antibody. When Lym-1, an IgG-2a murine antibody against human lymphoma, was used, yields of labeled immunoglobulin were decreased by protein or Chloramine-T concentrations less than 0.4 microgram/microliter and 0.8 microgram/microliter, respectively; denaturation of the immunoglobulin occurred when the Chloramine-T concentration was greater than 1.0 microgram/microliter. Optimum labeling occurred at pH 7-8 with deleterious effects when the pH was below 5 or above 10. An optimum method for labeling antibodies with multimillicurie amounts of 123I (less than one iodine atom per 100 antibody molecules) is described. Some of the observations derived from this study are also applicable to the preparation of treatment doses of 131I-labeled antibodies, wherein the amount of antibody can be a restrictive factor.

Antibodies, Monoclonal↗