Dosimetry of copper-64-labeled monoclonal antibody 1A3 as determined by PET imaging of the torso

We present biodistribution and dosimetry results for 64Cu-benzyl-TETA-MAb 1A3 from 15 human subjects injected with this tracer as determined by serial PET imaging of the torso. METHODS: PET imaging was used to quantify in vivo tracer biodistribution at two time points after injection. Absorbed dosimetry calculated using MIRD-11 and the updated MIRDOSE3 was compared with estimates obtained using rat biodistribution data. RESULTS: By measuring activity concentrations in the torso, and extrapolating for the whole body using standard organ and tissue volumes, we were able to account for 93% of the injected radiopharmaceutical over a range of imaging times from 0 to 36 hr postinjection. Based on PET imaging and the MIRD-11 schema, the liver and spleen are the critical organs with average absorbed doses of 0.12 and 0.10 mGy/MBq (0.44 and 0.39 rad/mCi). The revised MIRDOSE3 scheme yields similar values for these and other organs but also results in a dose of 0.14 mGy/MBq (0.53 rad/mCi) to the heart wall. In the rat, the large intestine is the critical organ at 0.14 mGy/MBq (0.52 rad/mCi), while liver and kidneys each receive 0.11 mGy/MBq (0.41 rad/mCi). Some disparities in absorbed doses determined by these methods are evident but are a result of dissimilar biodistributions in rats and humans. For most organs, rat extrapolated values are higher than the human measurements with PET. CONCLUSION: This study shows that torso PET imaging can quantitatively measure the whole-body biodistribution of a radiopharmaceutical as long as it has relatively slow pharmacokinetics.     

Five-year survival rates of melanoma patients treated by diet therapy after the manner of Gerson: a retrospective review

OBJECTIVE: Compare 5-year melanoma survival rates to rates in medical literature. DESIGN: Retrospective. SETTING: Hospital in Tijuana, Mexico. PATIENTS: White adult patients (N = 153) with superficial spreading and nodular melanoma, aged 25-72 years. INTERVENTION: Gerson's diet therapy: lactovegetarian; low sodium, fat and (temporarily) protein; high potassium, fluid, and nutrients (hourly raw vegetable/fruit juices). Metabolism increased by thyroid; calorie supply limited to 2600-3200 calories per day. Coffee enemas as needed for pain and appetite. MAIN OUTCOME MEASURE: 5-year survival rates by stage at admission. RESULTS: Of 14 patients with stages I and II (localized) melanoma, 100% survived for 5 years, compared with 79% of 15,798 reported by Balch. Of 17 with stage IIIA (regionally metastasized) melanoma, 82% were alive at 5 years, in contrast to 39% of 103 from Fachklinik Hornheide. Of 33 with combined stages IIIA + IIIB (regionally metastasized) melanoma, 70% lived 5 years, compared with 41% of 134 from Fachklinik Hornheide. We propose a new stage division: IVA (distant lymph, skin, and subcutaneous tissue metastases), and IVB (visceral metastases). Of 18 with stage IVA melanoma, 39% were alive at 5 years, compared with only 6% of 194 from the Eastern Cooperative Oncology Group. Survival impact was not assessed for stage IVB. Male and female survival rates were identical for stages I-IIIB, but stage IVA women had a strong survival advantage. CONCLUSIONS: The 5-year survival rates reported here are considerably higher than those reported elsewhere. Stage IIIA/B males had exceptionally high survival rates compared with those reported by other centers.     

Leucocyte interleukin-1-like activity in the common seal (Phoca vitulina) and grey seal (Halichoerus grypus)

Interleukin-1 (IL-1) is an important cytokine with predominantly proinflammatory activities, which have been characterized in many mammals. This study showed the production of IL-1-like bioactivity by cultured seal leucocytes. Increasing concentrations of lipopolysaccharide (LPS) (0-1 micrograms/ml) stimulated an increase in measurable IL-1-like activity in cell culture supernates. This activity increased for the first 24 h after LPS stimulation and the substance responsible had an apparent molecular weight of 17 kDa on gel filtration, similar to that described for other species. Specificity of the bioassay used was confirmed by blocking the bioactivity with an IL-1 receptor antagonist (IL-1 ra).     

Role of metabolism in ethyl carbamate-induced suppression of antibody response to sheep erythrocytes in female Balb/C mice

A possible role of metabolism by cytochrome P450 (P450) in ethyl carbamate-induced suppression of the antibody response to a T-cell-dependent antigen, sheep erythrocytes (SRBCs), was investigated in female Balb/C mice. When mice were treated with ethyl carbamate intraperitoneally for 14 consecutive days at 25, 50, 100, 200 and 400 mg/kg, the antibody response was significantly suppressed from 200 mg/kg. These doses also caused a decrease in thymus weight. An acute dosing of ethyl carbamate at 1 g/kg also caused not only a significant suppression of the antibody response, but also a decrease in thymus weight. The antibody response was most likely to be the IgM antibody response, which was demonstrated in a haemagglutination study. When mice were pretreated with phenobarbital (80 mg/kg) for 3 days to induce P450 enzymes, followed by administration of ethyl carbamate intraperitoneally for 7 consecutive days, the antibody response was more suppressed than in saline-pretreated controls. Moreover, a study using aminoacetonitrile, a P450 inhibitor, showed that the antibody response suppressed by ethyl carbamate was completely recovered by the inhibitor. The present results suggest that metabolism of ethyl carbamate by P450 may be the critical pathway to produce metabolites capable of suppressing the antibody response.     

Models for the effects of individual size and spatial scale on competition between species in heterogeneous environments

A spatially explicit model for competition with dispersal in a heterogeneous environment is used to study the effects of individual size and the spatial scale of the environment on the competitive interactions between species. The model is a Lotka-Volterra competition system with diffusion and with spatial variation in some coefficients. The coefficients in the model are taken to reflect a situation where the larger competitor typically disperses farther in unit time than the smaller and reproduces less rapidly, but has an advantage in contests or other forms of interference competition. The environment is assumed to be closed, i.e., it is assumed that individuals do not leave through the boundary. The environment is generally assumed to consist of a patch of favorable habitat surrounded by less favorable regions. The effects of spatial scale are studied by examining how the predictions of the model change as the size of the favorable patch is varied. The predictions turn out to be in qualitative agreement with the results of some empirical studies.