Direct <sup>99m</sup>Tc Labeling of Pegylated Liposomal Doxorubicin (Doxil) for Pharmacokinetic and Non-Invasive Imaging Studies

Bao, Ande; Goins, Beth; Klipper, Robert; Negrete, George R.; Phillips, William T.

doi:10.1124/jpet.103.059535

Cited by 115 publications

(115 citation statements)

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“…The new UAL method has major advantages compared to previous reported IAL methods, 4,[7][8][9][10][11][12] because of its simplicity, excluding the use of any ionophore. furthermore showed a dramatic increase in oil/water-partitioning of copper as pH was raised from 6.5 to 7.0.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11][12] So far, only a few ionophore assisted loading (IAL) procedures have been developed for liposomal PET imaging applications. 1,12,13 Despite the generally high loading efficiencies, high radionuclide retention, rapid loading kinetics and successful in vivo liposomal performance there are disadvantages of using transporter molecules such as ionophores or lipophilic chelators (hereafter referred to as ionophores as a common term) for remote loading of radionuclides into liposomes.…”

Section: Introductionmentioning

confidence: 99%

“…Common practice is therefore to use ionophores to increase the trans-membrane ion diffusion rate, and thereby improve the loading kinetics of charged ions such as radionuclides into liposomes. [7][8][9][10][11][12][13] Despite previous knowledge and findings within this field, the present work describes a novel loading method of the PET radionuclide 64 Cu 2+ into liposomes, excluding the use of ionophores (an unassisted loading). In this method, 64 Cu 2+ (or copper) is added to preformed liposomes entrapping a high affinity copper chelator (Figure 1, left).…”

Section: Introductionmentioning

confidence: 99%

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Remote Loading of ⁶⁴Cu²⁺ into Liposomes without the Use of Ion Transport Enhancers

Henriksen

Petersen

Hansen

et al. 2015

ACS Appl. Mater. Interfaces

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Due to low ion permeability of lipid bilayers, it has been and still is common practice to use transporter molecules such as ionophores or lipophilic chelators to increase trans-membrane diffusion rates and loading efficiencies of radionuclides into liposomes. Here, we report a novel and very simple method for loading the positron emitter 64 Cu 2+ into liposomes, which is important for in vivo positron emission tomography (PET) imaging. By this approach, copper is added to liposomes entrapping a chelator, which causes spontaneous diffusion of copper across the lipid bilayer where it is trapped. Using this method, we achieve highly efficient 64 Cu 2+ loading, high radionuclide retention, and favorable loading kinetics, excluding use of transporter molecule additives. We investigate the molecular coordination of entrapped copper using X-ray absorption spectroscopy, and demonstrate high adaptability of the loading method to different lipid formulations. We demonstrate high in vivo stability of 64 Cu-liposomes in a canine cancer model and evaluate tumor accumulation in mice using PET imaging. With this work, it is demonstrated that copper ions are capable of crossing a lipid membrane unassisted. This method is highly valuable for characterizing in vivo performance of liposome-based nanomedicine with great potential in diagnostic imaging applications.3

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Remote Loading of ⁶⁴Cu²⁺ into Liposomes without the Use of Ion Transport Enhancers

Henriksen

Petersen

Hansen

et al. 2015

ACS Appl. Mater. Interfaces

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“…Previous scintillation studies of liposome kinetics have involved radionuclides attached to the liposome surface using chelators covalently linked to lipid soluble anchors [22], or encapsulated the imaging probe inside the liposome hydrophilic cavity [23,24]. Here, in order to facilitate high-resolution pharmacodynamic measurements, we employ 18 F for PET trafficking of peptide-targeted liposomes (Figure 1), using an 18 [25].…”

Section: Introductionmentioning

confidence: 99%

Dynamic imaging of arginine-rich heart-targeted vehicles in a mouse model

Zhang

Kusunose²,

Kheirolomoom³

et al. 2008

Biomaterials

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Efficacious delivery of drugs and genes to the heart is an important goal. Here, a radiolabeled peptidetargeted liposome was engineered to bind to the heart, and the biodistribution and pharmacokinetics were determined by dynamic positron emission tomography in the FVB mouse. Efficient targeting occurred only with an exposed ligand and a dense concentration of peptide (6000 peptides/particle). Liposomes targeted with CRPPR or other arginine-rich peptides with an exposed guanidine moiety bound within 100 seconds after intravenous injection and remained stably bound. With CRPPRtargeted particles, the radioisotope density in the heart averaged 44 ± 9% injected dose per gram of tissue, more than 30 fold higher than in skeletal muscle. The rapid and efficient targeting of these particles can be exploited in drug and gene delivery systems and with dynamic positron emission tomography provides a model system to optimize targeting of engineered particles.

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“…Regardless of their predominant uptake by the mononuclear phagocyte system after i.v. administration (Bao et al 2004), liposomes show a selective accumulation in lymph nodes after local parenteral administration such as s.c., intratumoral, i.m., submucosal and i.p. injection (Oussoren & Storm 2001).…”

Section: Introductionmentioning

confidence: 99%

Effect of small-sized liposomal Adriamycin administered by various routes on a metastatic breast cancer model

Jh¹

2005

Endocrine Related Cancer

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The antitumor effects of small-sized liposomal Adriamycin (LADR) administered by various routes were investigated in rabbits bearing well-developed VX2 tumors in the mammary gland. Rabbits received s.c. or i.v., or s.c. combined with i.v., injections of LADR 6 weeks after tumor implantation. The i.v. route showed a significant inhibitory effect on breast tumors and distant metastases. In comparison, metastases in axillary and mediastinal lymph nodes were more efficiently inhibited after s.c. injection. LADR administered concurrently by both the i.v. and s.c. routes produced satisfactory therapeutic activities on both primary breast tumors and metastases in local-regional lymph nodes, lungs and liver, as shown by slowed growth rates, decreased mRNA expression of proliferating cell nuclear antigen, and extensive necrosis and apoptosis of tumor cells. It is concluded that smallsized LADR administered s.c. provides reliable efficacy on lymphatic metastases of breast cancer and that the addition of treatment by the s.c. route to that by the conventional i.v. route can be recommended as a promising procedure to enhance chemotherapeutic effects in patients with metastatic breast cancer.

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Direct ^99mTc Labeling of Pegylated Liposomal Doxorubicin (Doxil) for Pharmacokinetic and Non-Invasive Imaging Studies

Abstract: Pharmacokinetic and organ distribution studies of liposomal drugs in humans are a challenge. A direct labeling method using 99m

Cited by 115 publications

References 30 publications

Remote Loading of ⁶⁴Cu²⁺ into Liposomes without the Use of Ion Transport Enhancers

Remote Loading of ⁶⁴Cu²⁺ into Liposomes without the Use of Ion Transport Enhancers

Dynamic imaging of arginine-rich heart-targeted vehicles in a mouse model

Effect of small-sized liposomal Adriamycin administered by various routes on a metastatic breast cancer model

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Direct 99mTc Labeling of Pegylated Liposomal Doxorubicin (Doxil) for Pharmacokinetic and Non-Invasive Imaging Studies

Abstract: Pharmacokinetic and organ distribution studies of liposomal drugs in humans are a challenge. A direct labeling method using 99m

Cited by 115 publications

References 30 publications

Remote Loading of 64Cu2+ into Liposomes without the Use of Ion Transport Enhancers

Remote Loading of 64Cu2+ into Liposomes without the Use of Ion Transport Enhancers

Dynamic imaging of arginine-rich heart-targeted vehicles in a mouse model

Effect of small-sized liposomal Adriamycin administered by various routes on a metastatic breast cancer model

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Product

Resources

About

Direct ^99mTc Labeling of Pegylated Liposomal Doxorubicin (Doxil) for Pharmacokinetic and Non-Invasive Imaging Studies

Remote Loading of ⁶⁴Cu²⁺ into Liposomes without the Use of Ion Transport Enhancers

Remote Loading of ⁶⁴Cu²⁺ into Liposomes without the Use of Ion Transport Enhancers