111In-capromab pendetide: the evolution of prostate specific membrane antigen and the nuclear imaging of its 111In-labelled murine antibody in the evaluation of prostate cancer.

Each year, approximately 210,000 American men are diagnosed with prostate cancer and 41,800 die from the disease - numbers roughly equal to the incidence and mortality for breast cancer in women. Prostate cancer usually shows no symptoms in early stages, when it is most treatable. To detect the disease early, physicians usually recommend that every man 50 years and older have an annual examination consisting of a digital rectal examination and a prostate specific antigen (PSA) blood test. Conventional treatments such as surgical removal of the diseased prostate, external beam radiation, radioactive seed therapy and hormonal and/or chemotherapy treatment regimens are most successful for early stage prostate cancer and have limited effectiveness in advanced stages of the disease. For this reason, accurate staging of primary and recurrent prostate cancer is mandatory for proper therapeutic decisions. Nuclear medicine imaging of prostate cancer using the radiolabelled monoclonal antibody, (111)In-capromab pendetide, has proven useful in newly diagnosed patients with biopsy-proven prostate cancer in which there is high suspicion of distant metastatic disease and for prostatectomy patients with rising PSA levels and/or suspicion of recurrence or metastatic disease. Although not intended as a screening tool, it is used in conjunction with standard evaluation procedures for improved staging of patients. The monoclonal antibody, designated 7E11-C5, binds the prostate specific membrane antigen (PSMA) expressed on the surface of prostate epithelial cells and up-regulated in tumour cells. The sensitivity and specificity for prostate cancer involved lymph node detection has been reported as 62 to 75% and 72 to 86%, respectively, compared with sensitivities of 4% and 15% for computerised tomography and magnetic resonance imaging. (111)In-capromab pendetide imaging has proven to be an accurate, non-invasive tool for detecting and staging sites of recurrence in the post-prostatectomy patient as well as metastatic sites in the patient with newly diagnosed prostate cancer.

Induction of amphotericin B-specific antibodies for use in immunoassays.

High-titered antisera specific for amphotericin B (AmB) were induced by immunization with a protein conjugate of the D-lysyl AmB methyl ester. These polyclonal anti-AmB antibodies reacted preferentially with AmB or the AmB methyl ester and discriminated sharply between nystatin and AmB. A solid-phase radioimmunoassay was developed with radioiodinated immunoglobulin G fractions derived from the anti-AmB antisera. This assay was capable of detecting AmB in the sera in the same concentration range that is regularly achieved during AmB treatment of systemic fungal infections. This study demonstrated the feasibility of immunoassays in measuring the concentration of AmB in blood and tissue fluids.

The relationship between adjuvant and mitogenic effects of amphotericin methyl ester.

The antifungal polyene amphotericin B (AmB) and its methyl ester derivative (AME) both show potent murine immunostimulant as well as B-cell activating effects. Under certain experimental conditions, AME is a much more potent polyclonal B-cell activator (PBA) than AmB. Notable features of the murine B-cell stimulation induced by AME include: (i) High concentrations of AME (50-100 microgram/ml) are required and even at this level exhibit little or no spleen cell toxicity. (ii) Several lines of evidence suggest that the B-cell activating properties of AME are not involved in the cellular mechanism of adjuvant activity in vivo. (iii) There is a strong correlation between the magnitude of the in vitro PBA effects and the in vivo adjuvant effects of AME in a survey of different mouse strains. This evidence suggests that there is genetic control of the murine lymphoid cell-stimulatory effects of AME and that a small number of genes determines the responsive phenotype.