<p>A Radio-Nano-Platform for T1/T2 Dual-Mode PET-MR Imaging</p>

Abstract

Video abstractPoint your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: http://youtu.be/Me_QBfX7I3sPurpose: This study aimed to develop a chelate-free radiolabeled nanoparticle platform for simultaneous positron emission tomography (PET) and magnetic resonance (MR) imaging that provides contrast-enhanced diagnostic imaging and significant image quality gain by integrating the high spatial resolution of MR with the high sensitivity of PET. Methods: A commercially available super-paramagnetic iron oxide nanoparticle (SPION) (Feraheme ® , FH) was labeled with the [ 89 Zr]Zr using a novel chelate-free radiolabeling technique, heat-induced radiolabeling (HIR). Radiochemical yield (RCY) and purity (RCP) were measured using size exclusion chromatography (SEC) and radio-thin layer chromatography (radio-TLC). Characterization of the non-radioactive isotope 90 Zr-labeled FH was performed by transmission electron microscopy (TEM). Simultaneous PET-MR phantom imaging was performed with different 89 Zr-FH concentrations. The MR quantitative image analysis determined the contrast-enhancing properties of FH. The signal-to-noise ratio (SNR) and full-width half-maximum (FWHM) of the line spread function (LSF) were calculated before and after coregistering the PET and MR image data. Results: High RCY (92%) and RCP (98%) of the [ 89 Zr]Zr-FH product was achieved. TEM analysis confirmed the 90 Zr atoms adsorption onto the SPION surface (≈ 10% average radial increase). Simultaneous PET-MR scans confirmed the capability of the [ 89 Zr]Zr-FH nanoplatform for this multi-modal imaging technique. Relative contrast image analysis showed that [ 89 Zr]Zr-FH can act as a dual-mode T1/T2 contrast agent. For co-registered PET-MR images, higher spatial resolution (FWHM enhancement ≈ 3) and SNR (enhancement ≈ 8) was achieved at a clinical dose of radio-isotope and Fe. Conclusion: Our results demonstrate FH is a highly suitable SPION-based platform for chelate-free labeling of PET tracers for hybrid PET-MR. The high RCY and RCP confirmed the robustness of the chelate-free HIR technique. An overall image quality gain was achieved compared to PET-or MR-alone imaging with a relatively low dosage of [ 89 Zr]Zr-FH. Additionally, FH is suitable as a dual-mode T1/T2 MR image contrast agent.

Targeted PET/MRI Imaging Super Probes: A Critical Review of Opportunities and Challenges

“…In the chelator-free approach, 89 Zr can be directly conjugated to the feraheme (dextran-coated SPIONs) surface using heat-induced radiolabeling. 61 , 67 The sorption of germanium ions onto the iron oxide surface at pH from 4 to 8 has also been reported. 52 Radiolabeling of bimodal probes with non-metallic radionuclides such as 124 I or 11 C requires the formation of covalent bonds between the molecule and isotope.…”

“…Subsequently, T 1 but not T 2 rapidly dropped. 61 These results show the limited applicability of this probe when used at higher doses.…”

“… 23 , 34 , 36 , 49 , 50 , 52 , 59 , 62 , 66 To achieve colloidal stability, the surface of nanostructures was coated with dextran, which increased the probe’s stability in water, its biocompatibility, and its blood retention time. 39 , 47 , 51 , 57 , 61 , 67 , 68 In addition, the PAA (poly(acrylic acid) (PAA), 35 serum albumin, 37 and methoxy-PEG (MPEG) 58 were also used to increase the colloidal stability and water solubility.…”

“… 93 Even though the radiolabeling procedures take about 3 h, the RYs are not greatly affected by nuclear disintegration. Gholami et al 61 reported an RY of ~92% (89% after decay correction) for 89 Zr-labeled SPIONs. The efficiency of labeling a lipid-based bimodal probe with [ 89 Zr]Zr-hydroxide chloride was reported to be 99%, only at very low concentrations of both substrates, and decreased exponentially when the lipid concentration increased.…”

Positron annihilation localization by nanoscale magnetization

“…This can be attributed to the restriction of positron range by the strong nanoscale localization of magnetic field induced around the SPIONs www.nature.com/scientificreports/ in the presence of the external B 0 = 3 T in the PET-MRI scanner. These results suggest that SPIONs radiolabelled with suitable PET tracers 10,15,22 offer a novel approach to mitigating the well-known effect of positron range on spatial resolution in PET images 1,[3][4][5] . Thus, in PET-MRI, SPIONs can not only enhance MRI contrast, but can also enhance PET spatial resolution, with the potential to improve overall image quality compared to that achieved with either modality separately.…”