Pharmacokinetics and biodistribution of a small radioiodine labeled nerve growth factor fragment.
Nerve growth factor (NGF) exerts various actions on neuronal and non-neuronal tissues and has potential therapeutic utility, but difficulties in using the whole protein have stimulated interest in small NGF fragments. We radioiodinated a small cyclic peptide derived from NGF using the Bolton-Hunter method [125I-C(92-96)], and confirmed binding to high affinity NGF receptors by cross-linkage analysis. Pharmacokinetic characteristics in intravenously injected mice were T 1/2 alpha 5.2 min, T 1/2beta 121.3 min, clearance 11.8+/-0.5 ml/min, and volume of distribution 69.7+/-4.6 ml. Dose-proportionate increases in areas-under-curve and peak-concentrations indicated linear pharmacokinetics. Biodistribution data revealed that clinically relevant doses allowed C(92-96) accumulation sufficient to elicit biological responses in receptor expressing organs including the lungs, liver, spleen, and pancreas.
Jung
Kyung-Ho
KH
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim
Dong-Hyun
DH
Paik
Jin-Yung
JY
Ko
Bong-Ho
BH
Bae
Jun-Sang
JS
Choe
Yearn Seong
YS
Lee
Kyung-Han
KH
Kim
Byung-Tae
BT
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D051379:Mice; D008813:Mice, Inbred ICR; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000493:pharmacokinetics; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; D010455:Peptides; D017475:Receptors, Nerve Growth Factor; D020917:Receptor, trkA