Gadolinium‐labeled liposomes containing various amphiphilic Gd‐DTPA derivatives: Targeted MRI contrast enhancement agents for the liver

Kabalka, George W.; Davis, M.A.F.; Moss, T. H.; Buonocore, Edward; Hübner, Karl; Holmberg, Eric G.; Maruyama, Kazuo; Huang, Leaf

doi:10.1002/mrm.1910190231

Cited by 109 publications

(47 citation statements)

References 20 publications

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“…156 Different chelators and different hydrophobic anchors were tried for the preparation of 111 In, 99m Tc, Mn-, and Gd-liposomes. [157][158][159][160][161][162][163][164] In the case of MR imaging, for a better MR signal, all reporter atoms should be freely exposed for interaction with water. Membranotropic chelating agents -such as DTPA-stearylamine (DTPA-SA) 159 or DTPA-phosphatidyl ethanolamine (DTPA-PE) 156 -consist of the polar head containing a chelated paramagnetic atom, and the lipid moiety that anchors the metal-chelate complex in the liposome membrane.…”

Section: Targeting Tumors For Diagnostic Visualizationmentioning

confidence: 99%

Targeted pharmaceutical nanocarriers for cancer therapy and imaging

Torchilin

2007

AAPS J

670

428

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Section: Targeting Tumors For Diagnostic Visualizationmentioning

confidence: 99%

Targeted pharmaceutical nanocarriers for cancer therapy and imaging

Torchilin

2007

AAPS J

670

428

View full text Add to dashboard Cite

“…The white solid was stirred in water to dissolve any excess DTPA and stirred in boiling chloroform to dissolve any excess DTPA bis-anhydride and octadecylamine. Gd 3+ was then added to synthesize Gd-DTPA-BSA according to the procedure of Kabalka et al 7 The concentrations of Gd were determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES) (OPTIMA 4300DV, Perkin Elmer Ltd, Waltham, MA). The phase-transition temperature of Gd-DTPA-BSA was determined by differential scanning calorimetry on a Diamond DSC (Perkin Elmer Ltd, Waltham, MA).…”

Section: Synthesis Of Gd-dtpa-bsamentioning

confidence: 99%

“…[3][4][5][6] For example, Gd (III) [N,N-Bis-stearylamidomethyl-N′-amidomethyl] diethylenetriamine tetraacetic acid (Gd-DTPA-BSA), an amphipathic Gd complex, has been synthesized for incorporation into liposomes. 7 The resulting paramagnetic liposomes effectively enhanced T 1 -imaging. Optical imaging is another useful technology platform.…”

Section: Introductionmentioning

confidence: 99%

Folate receptor-targeted fluorescent paramagnetic bimodal liposomes for tumor imaging

Ding¹,

J²,

Huang³

et al. 2011

IJN

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Rationale and objective: Receptor-targeted delivery of imaging and therapeutic agents can lead to enhanced efficacy for both. Multimodality imaging offers unique advantages over traditional single modality imaging. Tumor marker folate receptor (FR)-targeted fluorescent paramagnetic bimodal liposomes were synthesized to co-deliver paramagnetic and fluorescence agents for magnetic resonance (MR) and optical bimodal imaging contrast enhancement. Materials and methods: Fluorescent and paramagnetic bimodal liposomes were synthesized with a mean diameter of 136 nm and a low polydispersity index. The liposomes incorporated folate-PEG 3350 -CHEMS for FR targeting, Gd(III)[N,N-Bis-stearylamidomethyl-N'-amidomethyl]diethylenetriamine tetraacetic acid (Gd-DTPA-BSA) for MR contrast, and calcein for fluorescence. To determine the specificity and efficiency of delivery, the liposomes were evaluated in FR-positive KB and HeLa cells and FR-negative A549 cells, which were analyzed by fluorescence microscopy, magnetic resonance imaging (MRI), and flow cytometry (FCM). Results: FR-specific and efficient cellular uptake of the FR-targeted bimodal liposomes was confirmed by fluorescence microscopy and by FCM. The mean fluorescence intensity (MFI) of KB cells treated with FR-targeted liposomes was 45× that of cells treated with nontargeted liposomes, and 18× that of cells treated with FR-targeted liposomes and excess folic acid (FA). The MFI of HeLa cells treated with targeted liposomes was 33× that of nontargeted liposomes, and was 16× that of the mixture of targeted liposomes and free FA. In contrast, the MFI of A549 cells treated with FR-targeted liposomes was nearly the same as those treated with nontargeted liposomes. The T 1 -weighted MR images of HeLa and KB cells incubated with FR-targeted liposomes had much higher signal intensity than those treated with nontargeted liposomes or free Gd-DTPA. Furthermore, the FR-targeting effect could be blocked by excess free FA. Conclusion: FR-targeted fluorescent paramagnetic bimodal liposomes provided a novel platform for bimodal tumor imaging and theranostic delivery.

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“…The more straightforward approach deals with the use of macromolecular conjugates containing many paramagnetic complexes, such as polylysine(Gd-DT-PA) n (22), dextran(Gd-DTPA) n (23), dendrimer(Gd-DT-PA) n (24), etc., bound to a synthon responsible for targeting. Analogously, one may use suitably functionalized liposomes (25) that can deliver a huge number of paramagnetic complexes. Such macromolecular systems may have major drawbacks related to the accessibility of the targeting sites when they are outside the blood circuit, and to their metabolic fate as well.…”

Section: Delivery Of Gd(iii) Complexes At the Site Of Interestmentioning

confidence: 99%

Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations

Aime

Cabella

Colombatto³

et al. 2002

Magnetic Resonance Imaging

328

275

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Can gadolinium III [Gd(III)] complexes be considered good candidates for magnetic resonance (MR)-molecular imaging studies? In this review article, we examine the principal issues that are the basis of successful use of Gd-based protocols in molecular imaging applications. High relaxivity is the primary requisite. Therefore, the design of such paramagnetic probes has to be pursued keeping in mind the relationships between structure, dynamics, and the relevant parameters involved in paramagnetic relaxation processes. Moreover, the limited number of target molecules on cellular membranes makes it necessary to define strategies aimed at delivering many Gd-containing moieties to the sites of interest. Examples are reported for the attainment of very high relaxivities for the design of new routes for pursuing the accumulation of small sized Gd(III) complexes at the targeting sites. An efficient cellular uptake of Gd-containing probes is the key step for attaining the visualization of targeted cells by MR imaging, and selected examples are reported. In this context, the problem of the assessment of the minimum amount of Gd(III) complexes necessary for the MR imaging-visualization of cells has been addressed by reporting the authors' observations on the cell-internalization of Gd(III) complexes. A particularly efficient delivery system is represented by Gd-loaded apoferritin, which allows the MR visualization of hepatocytes when the number of Gd-complexes per cell is 4 Ϯ 1 ϫ 10 7 . Finally, the potential of responsive systems is considered by outlining the exploitation of the amplification effect brought about by the action of a specific enzymatic activity on the relaxivity of a suitably functionalized Gd(III) complex. IT IS NOW WELL ESTABLISHED that magnetic resonance imaging (MRI) is the pre-eminent methodology among the various diagnostic modalities currently available, as it offers a powerful way to map structure and function in soft tissues by sampling the amount, flow, and environment of water protons in vivo. The intrinsic contrast can be augmented by the use of contrast agents (CA) in both clinical and experimental settings. Thus, the use of CA adds highly relevant physiological information to the superb anatomical resolution obtained in MR images. Most of the work with CAs has dealt with the use of gadolinium (III) [Gd(III)] complexes, because this metal ion couples a large magnetic moment with a long electron spin relaxation time.The new scenery of molecular imaging applications requires the development of a novel class of CAs characterized by a higher contrasting ability and improved targeting capabilities (1). In this survey, we intend to tackle some basic issues that are of fundamental importance for the use of Gd(III)-based systems in molecular imaging applications, namely: 1) actual understanding of the determinants of T 1 -relaxivity of Gd(III) complexes, and how to proceed to attain very high relaxivities; 2) how one may envisage efficient routes for the delivery of a high number of Gd(III) complexes a...

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Gadolinium‐labeled liposomes containing various amphiphilic Gd‐DTPA derivatives: Targeted MRI contrast enhancement agents for the liver

Cited by 109 publications

References 20 publications

Targeted pharmaceutical nanocarriers for cancer therapy and imaging

Targeted pharmaceutical nanocarriers for cancer therapy and imaging

Folate receptor-targeted fluorescent paramagnetic bimodal liposomes for tumor imaging

Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations

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