In vivo bioactivity and biodistribution of chemotactic peptide analogs in nonhuman primates.
The dose dependence of the effect of chemotactic peptide on peripheral leukocyte levels was measured in normal Rhesus monkeys. A 99mTc-labeled hydrazino nicotinamide (HYNIC) derivatized chemotactic peptide analog was used to study biodistribution and inflammation imaging in Rhesus monkeys. In normal animals the studies demonstrated that chemotactic peptide induced a clear dose-dependent reduction in peripheral leukocyte levels. The decrease in leukocyte number occurred almost immediately after injection and rapidly returned to baseline. Significant effects on differential WBC count, blood pressure, pulse rate or respiration rate were not detected. The lowest dose of peptide tested (10 ng/kg) had minimal effect on leukocyte level. The HYNIC derivatized peptide was prepared in excellent yield and purity, had biological activity similar to the native peptide and was readily labeled at specific activity of > 20,000 mCi/mumole. When approximately 0.5 mCi (< 2.0 ng/kg) of radiolabeled peptide was injected in monkeys with focal sites of mild sterile inflammation, a pattern of biodistribution similar to radiolabeled WBCs was observed and reductions in leukocyte levels were not detected. At 3 hr after injection, the site of inflammation was readily apparent with a target-to-background ratio of approximately 3:1. These studies demonstrate that radiolabeled chemotactic peptide analogs are effective agents for imaging sites of inflammation in monkeys. By radiolabeling at high specific activity, the effect of these reagents on peripheral leukocyte levels can be avoided.
Fischman
A J
AJ
Department of Radiology, Massachusetts General Hospital, Boston 02114.
Rauh
D
D
Solomon
H
H
Babich
J W
JW
Tompkins
R G
RG
Kroon
D
D
Strauss
H W
HW
Rubin
R H
RH
D000818:Animals; D002630:Chemotactic Factors / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000000981:diagnostic imaging; D007958:Leukocyte Count / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000493:pharmacokinetics; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D011877:Radionuclide Imaging; D013667:Technetium
D002630:Chemotactic Factors; D015609:Organotechnetium Compounds; C084659:formyl-norleucyl-leucyl-phenylalanyl-norleucyl-tyrosyl-lysine-DTPA; D009536:Niacinamide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013667:Technetium; D004369:Pentetic Acid