Claude F. Meares

Reagent and method for radioimaging leukocytes

Leukocytes are radioimmunoimaged by injecting patients with an immunoreactive nonleukocidal conjugate of an anti-leukocyte antibody and a gamma-emitting radioactive metal chelate, waiting for the conjugate to localize on the leukocytes, injecting the patient with an antibody to the conjugate to clear the blood of background nonlocalized conjugate, and visualizing the leukocytes by scintillation scanning.

Metabolizable 111in chelate conjugated anti-idiotype monoclonal antibody for radioimmunodetection of lymphoma in mice

The relative biological properties of 111In-labeled monoclonal antibodies (MoAb) coupled with a conventional bifunctional chelate (BC) and a new, enzyme metabolizable, bifunctional chelate (BCM) were investigated. A rat IgG2a MoAb against idiotype from a mouse B-cell lymphoma was utilized. Mice bearing B-cell lymphomas in the subcutaneous tissues of the flank were given IV-injections of labeled MoAb and imaged or killed for organ counting at 24 h or 48 h. Rat anti-dinitrophenyl IgG2a MoAb and non-specific polyclonal mouse IgG were used as controls. Compared to BC, the use of BCM resulted in a substantial decrease in blood background activity, a shorter biological half-life and an increase in tumor to blood ratio at the expense of a moderate decrease in absolute tumor uptake. The versatile chemistry of these C-1 substituted bifunctional chelates provides a variety of possible enzyme cleavable moieties for further investigation.

Bleomycin conjugates and method

A bleomycin conjugate for use in targeting a compound to a body tumor. The conjugate includes an oxidized bleomycin/cobalt(III) complex and the compound to be targeted joined to the complex through a monodentate cobalt/sulfur coordinate bond. Also disclosed are methods for preparing the conjugate, and for targeting the compound to a body tumor, for purposes of tumor radioimaging or therapy.

Conjugation of Bifunctional Chelating Agents to Bleomycin for Use in Nuclear Medicine

The affinity of bleomycin for tumorous tissue, coupled with its ability to chelate a variety of metal ions, has aroused considerable interest in its potential as a tumor-visualizing agent. The rationale behind this has been that the bleomycin chelate of a γ-ray emitting metal ion would localize in tumor tissue in vivo; the size and location of malignant tissue could then be determined for diagnostic purposes. 57Co-bleomycin was the first bleomycin chelate to be used clinically as a tumor-locating agent(1). Because of the 270-day radioactive half-life of 57Co, several other bleomycin-metal chelates have since been investigated (see Table 1).

Pretargeting: Improved Pharmacokinetics and Therapeutic Ratio

Pre-clinical studies of three step pretargeting of an anti-hapten mAb were done in BALB/c mice with KHJJ mouse adenocarcinoma. An 80% reduction in whole body radiation burden and a 10 fold increase in Therapeutic Ratio was achieved, compared to directly labeled mAb in this model.