Biodistribution and excretion of radioactivity after the administration of 166Ho-chitosan complex (DW-166HC) into the prostate of rat.
OBJECTIVE
The objective of this study was to determine the fate of the 166Ho-chitosan complex (DW-166HC) in rats by examining its absorption, distribution and excretion after administration into the prostate.


METHODS
About 100 microCi of DW-166HC [containing 0.1875 mg of Ho(NO3)3.5H2O and 0.25 mg of chitosan] was administered intraprostatically. The level of radioactivity in blood, urinary and faecal excretion, and radioactivity distribution were examined. To determine the effect of chitosan in DW-166HC, 166Ho nitrate alone [0.1875 mg of Ho(NO3)3.5H2O] was administered into the prostate of male rats, and radioactivity distribution was examined using whole-body autoradiography.


RESULTS
After administration of DW-166HC into the prostate, cumulative urinary and faecal excretion over the period 0-72 h was 0.35% and 0.11%, respectively. The radioactivity at the administration site was extremely high at all time points up to 144 h (>98% of injected dose). The small amount of radioactivity which did transfer from the administration site distributed mainly to the liver, spleen, kidney cortex and bone. Compared with the DW-166HC group, the group that received 166Ho nitrate alone displayed three- to fourfold higher levels of radioactivity in the main tissues, including liver, spleen, kidney cortex and bone, at 24 h after administration (P < 0.05).


CONCLUSIONS
The results of this study show clearly that most of the administered DW-166HC remained at the administration site. It is concluded that the chitosan complex may be used to retain 166Ho within a limited area in cancer of the prostate.
Seong
Seung Kyoo
SK
Pharmacology and Toxicology Lab, Central Research Laboratories, Dong Wha Pharmaceutical Co., Ltd., Anyang, South Korea.
Ryu
Jei Man
JM
Shin
Dong Hyuk
DH
Bae
Eun Jeong
EJ
Shigematsu
Akiyo
A
Hatori
Yasuhiko
Y
Nishigaki
Junko
J
Kwak
Cheol
C
Lee
Sang Eun
SE
Park
Kyong Bae
KB
D000818:Animals; D001822:Body Burden; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D004353:Drug Evaluation, Preclinical; D005243:Feces / Q000737:chemistry*; D006695:Holmium / Q000493:pharmacokinetics* / Q000652:urine*; D007267:Injections; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine*; D011467:Prostate / Q000378:metabolism*; D011829:Radiation Dosage; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000652:urine; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014915:Whole-Body Counting
C116411:DW 166HC; D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D002686:Chitin; D006695:Holmium