Intravenous technetium-99m labelled PEG-liposomes in horses: a safety and biodistribution study.
Abstract: Liposomes are phospholipid nanoparticles that extravasate at sites of increased vascular permeability. They have potential in equine medicine for targeted drug delivery and diagnostic imaging of infectious, inflammatory and neoplastic lesions. Objective: This study evaluates the safety and biodistribution of i.v. polyethyleneglycol(PEG) liposomes in normal horses. Methods: PEG-liposomes were prepared by the film hydration method and labelled using (99m) Tc-hexamethyl-propylene-amine-oxime. A single dose of 0.24 µmol/kg bwt (99m) Tc-PEG-liposomes and 2.4 µmol/kg bwt unlabelled PEG-liposomes was administered to 10 conscious horses via i.v. infusion at a rate of 6 µmol/min for the first 15 min and 60 µmol/min thereafter. Clinical parameters, haematology, plasma biochemistry and serum complement activity were monitored serially. Scintigraphic imaging was performed at 1, 12 and 21 h post infusion (PI). Six horses were subjected to euthanasia at 24 h PI. The percentage injected dose per kilogram of tissue was calculated for multiple organs. Results were analysed using repeated measures ANOVA. Results: Horses did not demonstrate adverse reactions during or after liposome infusion. There was a significant elevation in heart rate and respiratory rate at 20 and 25 min PI. No significant complement consumption was detected, although a trend for decreased total haemolytic complement values at 20 min PI was present. Scintigraphic studies revealed a prolonged vascular phase that lasted to 21 h PI, with a reproducible pattern of organ distribution. Biodistribution studies revealed the highest concentrations of radiopharmaceutical within the lung, kidney, liver and spleen. Conclusions: Intravenous liposome administration appears to be safe in horses. When administered in combination with PEG-liposomes, (99m) Tc-PEG-liposomes have long circulating characteristics and a reproducible pattern of organ distribution in horses. Conclusions: Radiolabelled liposomes may be useful for detecting infection, inflammation and neoplasia in the horse. Liposomes have significant potential for targeted drug delivery in the horse. This study establishes the scintigraphic findings and tissue distribution of 99mTc-PEG-liposomes after i.v. administration in healthy horses.
© 2011 EVJ Ltd.
Publication Date: 2011-06-23 PubMed ID: 21696436DOI: 10.1111/j.2042-3306.2011.00403.xGoogle Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research introduces a study looking into the safety and biodistribution of polyethyleneglycol (PEG) liposomes in horses. The study found that when injected intravenously, these liposomes appear safe and show a specific pattern of distribution in the horses’ bodies, potentially proving useful for targeted drug delivery and disease detection.
Objective and Methods
- The key aim of this research was to gauge the safety and assess how PEG-liposomes distribute within a horse’s body when administered intravenously.
- To perform this study, the PEG-liposomes were created through a process known as the film hydration method and subsequently labelled with technetium-99m, a common radiopharmaceutical used in medical imaging.
- A combination of technetium-99m labelled PEG-liposomes and unlabelled PEG-liposomes were administered to 10 conscious horses via intravenous infusion. The infusion was given at a rate of 6 µmol/min for the first 15 minutes, and then at a rate of 60 µmol/min afterwards.
- Different parameters such as heart rate, respiratory rate, hematology, plasma biochemistry, and serum complement activity were monitored at various intervals. Scintigraphic (a diagnostic test in nuclear medicine) imaging was performed 1, 12, and 21 hours post intravenous infusion to assess the distribution of the PEG-liposomes in the horses’ bodies.
Results
- No adverse reactions were reported in the horses during or after the infusion of the PEG-liposomes.
- A noticeable raise in heart rate and respiratory rate was observed at the 20 and 25-minute marks post-infusion.
- There were trends indicating decreased total haemolytic complement values (part of the immune response) at 20 minutes post-infusion, but no significant complement consumption was detected otherwise.
- Scintigraphic images showcased a prolonged vascular phase lasting to 21 hours post-infusion, and revealed a clear pattern of organ distribution with a high concentration of radiopharmaceutical within the lung, kidney, liver, and spleen.
Conclusions
- The study concluded that the administration of PEG-liposomes intravenously is safe in horses. The technetium-99m labelled liposomes circulated for a long time in the body and showed reliable organ distribution patterns.
- It was highlighted that these radiolabelled liposomes can potentially be used for identifying infections, inflammations, and tumors in horses.
- The possibility of using PEG-liposomes for targeted drug delivery in horses was also emphasized in the conclusion, making this a potentially significant development in veterinary medicine. This research sets a foundation for interpreting findings and tissue distribution of technetium-99m PEG-liposomes after intravenous administration in healthy horses.
Cite This Article
APA
Underwood C, van Eps AW, Ross MW, Laverman P, van Bloois L, Storm G, Schaer TP.
(2011).
Intravenous technetium-99m labelled PEG-liposomes in horses: a safety and biodistribution study.
Equine Vet J, 44(2), 196-202.
https://doi.org/10.1111/j.2042-3306.2011.00403.x Publication
Researcher Affiliations
- Department of Clinical Studies New Bolton Center, Kennett Square, University of Pennsylvania, School of Veterinary Medicine, PA, USA. claire.underwood@uqconnect.edu.au
MeSH Terms
- Animals
- Female
- Horses / metabolism
- Injections, Intravenous
- Liposomes / administration & dosage
- Liposomes / adverse effects
- Liposomes / chemistry
- Liposomes / pharmacokinetics
- Male
- Polyethylene Glycols / administration & dosage
- Polyethylene Glycols / adverse effects
- Polyethylene Glycols / chemistry
- Polyethylene Glycols / pharmacokinetics
- Radiopharmaceuticals / administration & dosage
- Radiopharmaceuticals / adverse effects
- Radiopharmaceuticals / chemistry
- Radiopharmaceuticals / pharmacokinetics
- Technetium Tc 99m Exametazime / administration & dosage
- Technetium Tc 99m Exametazime / adverse effects
- Technetium Tc 99m Exametazime / chemistry
- Technetium Tc 99m Exametazime / pharmacokinetics
- Tissue Distribution
Citations
This article has been cited 5 times.- Man F, Gawne PJ, T M de Rosales R. Nuclear imaging of liposomal drug delivery systems: A critical review of radiolabelling methods and applications in nanomedicine. Adv Drug Deliv Rev 2019 Mar 15;143:134-160.
- Tsopelas C. Radiotracers used for the scintigraphic detection of infection and inflammation. ScientificWorldJournal 2015;2015:676719.
- Salgueiro MJ, Zubillaga M. Strategic Objectives of Nanotechnology-Driven Repurposing in Radiopharmacy-Implications for Radiopharmaceutical Repurposing (Beyond Oncology). Pharmaceutics 2025 Sep 3;17(9).
- Salgueiro MJ, Portillo M, Tesán F, Nicoud M, Medina V, Moretton M, Chiappetta D, Zubillaga M. Design and development of nanoprobes radiolabelled with (99m)Tc for the diagnosis and monitoring of therapeutic interventions in oncology preclinical research. EJNMMI Radiopharm Chem 2024 Oct 29;9(1):74.
- Yang B, Kou R, Wang H, Wang A, Wang L, Sun S, Shi M, Zhao S, Wang Y, Wang Y, Wu J, Wu F, Yang F, Qu M, Yu W, Gao Z. Improved efficacy of cisplatin delivery by peanut agglutinin‑modified liposomes in non‑small cell lung cancer. Int J Mol Med 2024 Aug;54(2).
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