Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250.

Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG250) in renal cell carcinoma (RCC) patients indicated the potential use of this antibody for radioimmunotherapy. Here we report on a phase I activity dose escalation study to determine the safety, the maximum tolerable dose (MTD), and the possible therapeutic potential of 131I-labeled cG250 in patients with progressive metastatic RCC. All patients (n = 12) received a diagnostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of 131I. If accumulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 labeled with a high dose of 131I was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m2. If no dose-limiting toxicity occurred, the study continued at the next dose level (555 MBq/m2 increase). Most patients experienced mild nausea without vomiting. No other complaints were reported during hospitalization. In two of two patients who received a dose of 2775 MBq/m2, grade IV hematological toxicity was observed, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq/m2. In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) was achieved, whereas another patient (2220 MBq/m2) showed a partial response that is ongoing (>9 months). The minor responses observed in this phase I trial in patients with an advanced stage of RCC are encouraging and warrant further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.

The effect of positive expiratory pressure versus forced expiration technique on tracheobronchial clearance in chronic bronchitics.

In a randomized cross-over trial, including a control measurement the effect of positive expiratory pressure (PEP) and forced expiration technique (FET) on tracheobronchial clearance was evaluated in eight chronic bronchitics with abundant sputum production (mean, 32 g/day). PEP consisted of PEP-mask breathing interspersed with breathing exercises, huffing, and coughing. FET consisted of postural drainage, breathing exercises, huffing, and coughing. Clearance was measured with a radio-aerosol technique. At 40 min after the start of therapy the mean clearance, expressed as percentage of the amount of radioactivity present at the start of therapy, was 32% after PEP, 53% after FET, and 15% in the control run. The difference between PEP, FET, and control was statistically significant (p less than 0.02). Sputum production during PEP and FET was larger than during the equivalent period of time in the control run. It is concluded that FET is more effective than PEP in enhancing tracheobronchial clearance.

99mTc-pertechnetate uptake measurement in the rabbit knee-joint. II. Kinetics of 99mTcO-4 in normal and arthritic rabbit knee-joints.

The kinetics of 99mTechnetium pertechnetate (99mTcO-4) in the rabbit knee-joint were studied by external counting of the radio-isotope after intravenous injection. We studied joints with antigen-induced arthritis in the acute and chronic phase of joint inflammation as well as non-inflamed joints. In both inflamed and non-inflamed joints, a rapid increase in radioactivity was followed by a plateau lasting for at least one hour. The time needed to reach 95% of the plateau count rate (tp) was significantly increased in inflamed as compared with non-inflamed knee-joints. Moreover, tp values were significantly higher in acutely than in chronically inflamed joints. No correlation was found between 99mTcO1 uptake and tp values. The study of kinetics of 99mTcO-4 in the rabbit knee-joint provides information additional to quantitation of inflammation by 99mTcO-1 uptake measurements, since kinetic data characterize the type of joint inflammation.

Antigen handling in antigen-induced joint inflammation: kinetics of a second intra-articularly injected dose of antigen in an already established antigen-induced joint inflammation.

The fate of a second intra-articularly (i.a.) injected dose of bovine serum albumin (BSA) in an already established BSA-induced knee-joint inflammation was compared with that of a paired first arthritis-inducing injection of the same dose of BSA into the contralateral knee of immunized rabbits. External counting of i.a. radiolabelled BSA indicated more rapid initial elimination but approximately two-fold increase in long-term retention of BSA after a second i.a. injection as compared with a first one. Direct counting of dissected joint structures confirmed these data and localized the retained BSA predominantly in hyaline articular cartilage, menisci and ligaments, both after a first and after a second injection. Since the protocol used in these studies per se excluded systemic factors as possible determinants of the difference in antigen retention observed, local alterations in the already inflamed joint caused this difference. Control studies indicated that both humoral immune factors and non-specific inflammatory changes within the chronically inflamed joint determine the phenomenon. Local alterations in an immune-induced chronically-inflamed joint increase its antigen-binding capacity, a mechanism of possible relevance to the chronic course and the occurrence of exacerbations characteristic of some forms of human arthritis.