PET-MR Imaging of Cancer

Targeted liposome delivers PET probe and MR contrast agent for enhanced tumor imaging

Dual modality imaging combining positron emissions tomography (PET) and magnetic resonance (MR) imaging can improve diagnosis and disease tracking by providing concurrent, high-resolution anatomical and functional views. MR imaging provides good tissue contrast while avoiding radiation exposure of CT.  PET provides functional imaging of targeted tissues, such as tumors, within the MR anatomical context, for non-invasive diagnosis and disease monitoring.

To facilitate concurrent PET and MR imaging in oncology, Abou et al. demonstrate a new technique to load liposomes with simultaneous paramagnetic and radiopharmaceutical probes, and target them to a specific tumor type.

(89)Zr-labeled paramagnetic octreotide-liposomes for PET-MR imaging of cancer.
Abou DS, Thorek DL, Ramos NN, Pinkse MW, Wolterbeek HT, Carlin SD, Beattie BJ, Lewis JS.
Pharm Res. 2013 Mar;30(3):878-88. PubMed Central: PMC3578092

Liposomes are well established as low-toxicity, biodegradable vehicles for pharmaceutical delivery. Covalent attachment of polyethylene glycol (PEG) - or pegylation - ensures a long circulation time. Abou et al. developed liposomes carrying both the common MR T1 contrast agent gadolinium (Gd) and the positron-emitting radionucleotide 89-zirconium (89Zr). The researchers conjugated the liposomes with the peptide octreotide to selectively target neuroendocrine tumors via human somatostatin receptor subtype 2 (SSTr2).

After confirming successful labeling of the liposomes in vitro, the authors performed PET and MR imaging of mice carrying both wild-type and SSTr2-positive tumors. The researchers acquired MR images on a Bruker 4.7 T 40 cm bore scanner equipped with 400 mT/m shielded gradients, using a 36-mm ID quadrature resonator for excitation and detection. The team localized tumors in T2 scout images before taking five, 1-mm-thick T1-weighted axial gradient-echo images across the tumor. Using a deionized water phantom as a signal intensity reference, they quantified tumor contrast using ImageJ software.

One animal in each group was given a CT scan for CT/PET/MR co-registration. PET and CT images were co-registered based on bed position; MR images were co-registered based on bone visualization.

The authors successfully demonstrated the use of their liposome-based dual contrast agent with Bruker MR technology to acquire high-resolution images of SSTr2-positive tumors in mice with detailed anatomical context. The newly established technique could be used to deliver other imaging or therapeutic agents for multimodal imaging, and to provide imaging of liposome-delivered drug actions in vivo.

Characterization of OCT coupled to DSPE-PEG2000-CO2H

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Characterization of OCT coupled to DSPE-PEG2000-CO2H (a and b) and to LPs (c and d). (a) C4-HPLC chromatogram of OCT and DSPE-PEG2000-CO2H coupling performed at pH 6 with EDC and S-NHS and acquired using electrospray ionization-QTOF-MS (ESI) and UV-280 nm

 

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