Correlation between radioactivity and chemotherapeutics of the 111In-VNB-liposome in pharmacokinetics and biodistribution in rats

Abstract

Background The combination of a radioisotope with a chemotherapeutic agent in a liposomal carrier (ie, Indium-111-labeled polyethylene glycol pegylated liposomal vinorelbine, [ 111 In-VNB-liposome]) has been reported to show better therapeutic efficiency in tumor growth suppression. Nevertheless, the challenge remains as to whether this therapeutic effect is attributable to the combination of a radioisotope with chemotherapeutics. The goal of this study was to investigate the pharmacokinetics, biodistribution, and correlation of Indium-111 radioactivity and vinorelbine concentration in the 111 In-VNB-liposome. Methods The VNB-liposome and 111 In-VNB-liposome were administered to rats. Blood, liver, and spleen tissue were collected to determine the distribution profile of the 111 In-VNB-liposome. A liquid chromatography tandem mass spectrometry system and gamma counter were used to analyze the concentration of vinorelbine and radioactivity of Indium-111. Results High uptake of the 111 In-VNB-liposome in the liver and spleen demonstrated the properties of a nanosized drug delivery system. Linear regression showed a good correlation ( r = 0.97) between Indium-111 radioactivity and vinorelbine concentration in the plasma of rats administered the 111 In-VNB-liposome. Conclusion A significant positive correlation between the pharmacokinetics and biodistribution of 111 Indium radioactivity and vinorelbine in blood, spleen, and liver was found following administration of the 111 In-VNB-liposome. The liposome efficiently encapsulated both vinorelbine and Indium-111, and showed a similar concentration-radioactivity time profile, indicating the correlation between chemotherapy and radiotherapy could be identical in the liposomal formulation.

Therapeutic Efficacy Evaluation of Pegylated Liposome Encapsulated With Vinorelbine Plus 111In Repeated Treatments in Human Colorectal Carcinoma With Multimodalities of Molecular Imaging

“…In 2008, our team loaded liposomes with the radioactive 111 In and the chemotherapeutic VNB and compared the therapeutic effects of them with other potential combinations (39). In 2012, the overall efficacies of the 111 In-VNB-liposomes were investigated in a rat model with a perfect correlation between the pharmacokinetics and biodistribution (52). In the current study, we made a further modification by reducing the dose of the chemotherapeutic drugs from 5 mg/kg to 3 mg/kg and re-evaluated the overall efficacy from single dose to multiple doses.…”

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

“…Because vinorelbine is well known to cause venous irritation and phlebitis when directly administered intravenously, [ 89 - 92 ] new drug delivery systems are urgently required. [ 89 - 93 ]…”