Molecular imaging analysis of intestinal insulin absorption boosted by cell-penetrating peptides by using positron emission tomography.
Molecular imaging technique by use of positron emission tomography (PET) is a noninvasive tool that allows one to quantitatively analyze the function of endogenous molecules and the pharmacokinetics of therapeutic agents in vivo. This technique is expected to be useful for evaluating the effectiveness of diverse drug delivery systems. We demonstrated previously that intestinal insulin absorption is increased significantly by coadministration of cell-penetrating peptides (CPPs), which are taken up effectively by several cells. However, the distribution behavior of insulin whose absorption is increased by CPPs is not clear. We used PET imaging and quantitatively analyzed the intestinal absorption and subsequent distribution of insulin and the effect of CPPs on its absorption and distribution. An unlabeled insulin solution containing tracer insulin, (68)Ga-DOTA-insulin, was administered with or without CPPs into a rat ileal closed loop. PET imaging showed that the CPPs, particularly D-R8 and L-penetratin, significantly increased the (68)Ga-DOTA-insulin level in the liver, kidney, and circulation. After absorption from the intestine, the (68)Ga-DOTA-insulin passed rapidly through the liver and accumulated in the kidney. The increase in the hepatic and renal distribution of (68)Ga-DOTA-insulin by each CPP coadministration was similar manner as that in intestinal absorption, suggesting that the increased accumulation of insulin in the liver and kidney induced by coadministration of CPPs was associated with the increased intestinal absorption of insulin. This is the first study to show that PET imaging enables one to quantitatively analyze the distribution behavior of intestinally absorbed insulin in several organs. This imaging methodology is likely to be useful for developing effective drug delivery systems targeted to specific organs.
Kamei
Noriyasu
N
Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
Morishita
Mariko
M
Kanayama
Yousuke
Y
Hasegawa
Koki
K
Nishimura
Mie
M
Hayashinaka
Emi
E
Wada
Yasuhiro
Y
Watanabe
Yasuyoshi
Y
Takayama
Kozo
K
D000818:Animals; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D005682:Gadolinium; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007082:Ileum / Q000000981:diagnostic imaging / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000000981:diagnostic imaging*; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley
D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011868:Radioisotopes; D005682:Gadolinium