99mTc-Fanolesomab: affinity, pharmacokinetics and preliminary evaluation.

Localization of infection is critical for both diagnosis and treatment. Several radioactive compounds such as (67)Gallium citrate, (111I)ndium and (99m)Technetium-labeled leukocytes, peptides and antibodies have been used to localize sites of bacterial infection and phlegmons when anatomical imaging techniques failed. With labeled leukocytes the major concern besides the cost, was the in vitro procedure requiring more than 2 h and trained personnel to handle blood samples. Such limitations paved the way for the emergence of new agents like human immunoglobulin, interleukin-1, peptides and monoclonal antibodies. Following the intensive study of 10 monoclonal antibodies the anti SSEA-1 antibody specific for CD15 antigen was found to have a high Kd value of 1.6x10(-11) M for human neutrophils. Labeling of anti CD15 antibody (NeutroSpec) with (99m)Tc and its FDA approval was a boon to diagnostic imaging as it promised to eliminate many of the well known drawbacks of the in vitro WBC labeling. This antibody has a large number of antigenic binding sites: 5.1x10(5) per circulating human neutrophil. It has been established that very little CD15 antigen is expressed on the other blood cell lines. Upon intravenous administration to patients there was no adverse reaction except in those with underlying cardiovascular compromise or chronic pulmonary obstructive disease. Another advantage is that, this particular monoclonal antibody has not produced significant human antimouse antibody in research volunteers and patients. Twenty-four hour imaging, SPECT or planar was not required. The following pages describe the various stages of the research activity carried out towards NeutroSpec.

Turnover of cyclic adenosine-5'-monophosphate is elevated in skeletal muscle of vitamin E-deficient rabbits.

Two sets of experiments were performed to investigate the nonantioxidant functions of alpha-tocopherol. Eighteen rabbits in the first set and 48 rabbits in the second set were equally divided into three groups. The first group received a basal tocopherol-deficient diet supplemented with all-rac-alpha-tocopherol for 3 wk and the second group was fed the basal diet. The third group received vitamin E supplementation for 1 wk after 2 wk of consuming a tocopherol-deficient diet. In the first set of animals, skeletal muscle concentration, metabolism and turnover of various adenine nucleotides were measured by incubating the muscles of the three groups with [8-3H]adenine. The second set of experiments investigated in vivo concentration of various adenine nucleotides before incubation with radioactive substrate and quantity of newly formed adenine nucleotides after incubation with four different specific radioactive substrates: [8-14C]ATP; [8-14C]cAMP; [8-14C]5'AMP and [8-14C]adenosine. The results expressed per milligram of DNA were compared between the tocopherol-supplemented and tocopherol-deficient rabbits. Cyclic-AMP concentration (measured after a 2-h incubation with [8-3H]adenine) was lower and 5'-AMP concentration was very high in the tocopherol-deficient rabbits. The results of incorporation studies indicated that the turnover of ATP + ADP, cAMP, 5'-AMP and adenosine was higher in the tocopherol-deficient rabbits. Administration of tocopherol to tocopherol-deficient rabbits restored the turnover of cAMP to nearly normal values. These observations provided new insights concerning nonantioxidant functions of alpha-tocopherol.

Dosimetry of iodine-131 ethiodol in the treatment of hepatoma.

The in vivo distribution and kinetics of [131I]Ethiodol injected through the hepatic artery have been measured on a group of four patients with hepatocellular carcinoma. The [131I]Ethiodol was distributed predominantly in the liver (70-90%) and lungs (10-20%) and was selectively concentrated and retained in the patients with massive and multinodular hepatomas with approximately 10% of the administered activity localizing in tumor. The radioactivity in the blood 2 hr postinjection was less than 0.1% and was never higher than 0.9% of the administered activity. The radioactivity cleared from normal liver tissue with an effective half-life of approximately 4 days while the clearance time from the tumor was 20-25% longer. Activity in the lungs initially increased and then cleared with a 5-day effective half-life. Based on these measurements, the estimated dose per mCi of [131I]Ethiodol administered is 31 rad to the liver, 22 rad to the lungs, 1.9 rad to the total body and 239 rad to a 4-cm diameter tumor. These results suggest that [131I]Ethiodol has the potential to deliver curative radiation doses to hepatomas with acceptable radiation burdens to normal tissues.

Brain mRNA translatability in rats: changes during long-term dietary restriction in the developmental period of life.

We studied the effects of graded dietary restriction on the amount and translatability of messenger RNA (mRNA) molecule coding for brain proteins during the developmental period of life. Control experiments were performed on newborn, 1-, 3-, 6- and 27-week-old rats, whereas the dietary restriction studies, involving 10, 30 or 50% food deprivation, were conducted on weanling rats for periods of 3 or 24 weeks. Graded dietary restriction for 3 or 24 weeks caused a progressive reduction of the amount and translatability of mRNA in the rat brain. Complementary DNA (cDNA) probe and hybridization studies with [3H]cDNA revealed that food deprivation elicited a shorter species of mRNA or shorter sequences of the same species of mRNA coding for brain proteins and that not all polyadenylates mRNA [poly(A)+ mRNA] sequences found in control rats were present in the dietary-restricted animals. Furthermore, it appeared that food deprivation produced a shorter species of pre-mRNA via decreased polynucleotide elongation. The mRNA content of 27-week-old rat brains increased 12.5 times in comparison to newborns, representing an augmentation that was progressive and related to the developmental period of life of the animals. The translatability of mRNA was enhanced in the brain of 3-week-old rats, as compared to 1-week-old pups, and did not show any change thereafter. From these studies, it can be concluded that graded dietary restriction considerably modified the metabolism of mRNA in the rat brain, whereas minor alterations occurred during the developmental period of life in control animals.