Magnetic Resonance Imaging of Tumor with a Self-Traceable Phosphorylcholine Polymer

Abstract

Polymers are concentration-amplified with respect to the monomeric units. We show here that a phosphorylcholine polymer enriched with (13)C/(15)N at the methyl groups is self-traceable by multiple-resonance (heteronuclear-correlation) NMR in tumor-bearing mice inoculated with the mouse rectal cancer cell line (colon 26). Preliminary measurements indicated that the present polymeric nanoprobe was satisfactorily distinguished from lipids and detectable with far sub-micromolar spectroscopic and far sub-millimolar imaging sensitivities. Detailed ex vivo and in vivo studies for the tumor-bearing mice administered the probe with a mean molecular weight of 63,000 and a mean size of 13 nm, revealed the following: (1) this probe accumulates in the tumor highly selectively (besides renal excretion) and efficiently (up to 30% of the injected dose), (2) the tumor can thus be clearly in vivo imaged, the lowest clearly imageable dose of the probe being 100 mg/kg or 2.0 mg/20-g mouse, and (3) the competition between renal excretion and tumor accumulation is size-controlled; that is, the larger (higher molecular-weight) and smaller (lower molecular-weight) portions of the probe undergo tumor accumulation and renal excretion, respectively. The observed size dependence suggests that the efficient tumor-targeting of the present probe is stimulated primarily by the so-called enhanced permeability and retention (EPR) effect, that is, size-allowed invasion of the probe into the tumor tissue via defective vascular wall. Self-traceable polymers thus open an important area of magnetic resonance imaging (MRI) of tumors and may provide a highly potential tool to visualize various delivery/localization processes using synthetic polymers.

Spherical Polyelectrolyte Brushes as a Novel Platform for Paramagnetic Relaxation Enhancement and Passive Tumor Targeting

“…Hybrid materials have emerged as a class of promising materials in a variety of application fields, such as drug delivery, bioimaging, and tumor targeting . The material size, structure, and properties are facilely and precisely controlled, with multiple functionalities expressed in one individual material.…”

Polymeric 1H MRI Probes for Visualizing Tumor In Vivo

“…We have successfully developed a zwitterionic phosphorylcholine polymer ( 13 C/ 15 N-PMPC) probe enriched with 13 C/ 15 N at the methyl group for a probe-targeted multiple-resonance MR imaging of tumor in mice. [48] Although phosphorylcholine polymers have recently received increasing attention in terms of their high biocompatibility, [49] this 13 C/ 15 N-PMPC probe Figure 7. a) Catabolic reaction of 13 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 developed by us exhibited the otherwise unique characteristics.…”

Supramolecular Complexation in Biological Media: NMR Study on Inclusion of an Anionic Tetraarylporphyrin into a Per‐O‐Methylated β‐Cyclodextrin Cavity in Serum, Blood, and Urine

“…Isotope-labeling with NMR-active nuclei ( 13 C, 15 N, or 2 H) is aw ell-established methodu sed in the detection of the biomolecules of interest, such as sugars, lipids, and proteins, in cells or organs to monitor their structures, biodistribution, and/or metabolic byproducts. [25][26][27][28] To the best of our knowledge, however,N MR observation for the host-guestc omplexes of CDs in biologically crowded mediah as not been carried out yet. In this paper,w ef irst describe the synthesis and characterization of isotope-labeled 13 C-TMCD.…”

“…Then, we planned to synthesize an isotope‐labeled TMCD ( 13 C‐TMCD) bearing O 13 CH 3 groups at the 2‐, 3‐, and 6‐positions of the glucopyranose units. Isotope‐labeling with NMR‐active nuclei ( 13 C, 15 N, or 2 H) is a well‐established method used in the detection of the biomolecules of interest, such as sugars, lipids, and proteins, in cells or organs to monitor their structures, biodistribution, and/or metabolic byproducts . To the best of our knowledge, however, NMR observation for the host‐guest complexes of CDs in biologically crowded media has not been carried out yet.…”