Methods for magnetic resonance imaging of nanoconstructs and uses thereof
Methods for imaging magnetic resonance imaging (MRI) agents containing nanoconstructs therein using diffusion-weighted fast-spin echo (FSE) or gradient-and-spin echo (GRASE) processes are described herein.
1 . A method of imaging a magnetic resonance imaging (MRI) agent, the method comprising:
(a) administering the MRI agent to a subject, wherein the MRI agent comprises nanoconstructs each having a plurality of equivalent protons and an average molecular weight in a range of about 300 Da to about 300 kDa, and the nanoconstructs each have a T2 relaxation time greater than at least about 250 ms;
(b) using an MRI device to obtain a nuclear magnetic resonance scan of the that selectively images the nanoconstructs, wherein (b) comprises:
(i) scanning the subject with the MRI device, using
a signal acquisition bandwidth ranging from at least about 2 kHz to about 200 KHz and
greater than 8 spin echoes, so that signals from both (A) the plurality of equivalent nanoconstruct protons and (B) water protons are obtained; and
(ii) applying diffusion filtering to suppress the water proton signals from the scan,
so that the nuclear magnetic resonance scan that selectively images the nanoconstructs is obtained.
2 . The method of claim 1 , wherein the nanoconstructs each have a translational diffusion coefficient of less than about 2×10 −10 m 2 s −1 .
3 . The method of claim 1 , wherein (iii) comprises obtaining at least 3 gradient echoes.
4 . The method of claim 1 , wherein each of the nanoconstructs has an average molecular weight in a range of about 3 kDa to about 300 kDa.
5 . The method of claim 1 , wherein the T2 relaxation time is from about 550 ms to about 900 ms.
6 . The method of claim 1 , wherein the signal acquisition bandwidth is about 2 to about 50 KHz or about 5 to about 100 KHz.
7 . The method of claim 1 , wherein at least 16 spin echoes are obtained during (b).
8 . The method of claim 1 , wherein the plurality of equivalent protons comprises about 30 to 27,000 protons, 200 to about 15,000 protons, or about 200 to about 10,000 protons.
9 . The method of claim 1 , wherein each of the nanoconstructs comprises a linear or multi-armed polyethylene glycol (PEG).
10 . The method of claim 9 , wherein each of the nanoconstructs comprises one or more additives associated to the multi-armed PEG.
11 . The method of claim 10 , wherein the one or more additives comprise an active agent selected from the group consisting of targeting agents, therapeutic agents, chemotherapeutic agents, photosensitizer agents, sonosentizer agents, imaging agents, diagnostic agents, photoacoustic agents, theranostic agents, and combinations thereof.
12 . The method of claim 10 , wherein the one or more additives comprises an active agent selected from the group consisting of methylene blue, chlorin e6 (Ce6), coomassie blue, gold, a tetrapyrrole compound, a cyanine dye, a porphyrin, a chlorin, phthalocyanine, IR700 and derivatives thereof, a bacteriochlorin, HPPH, TOOKAD, LUZ 11, BC19porphyrin, a phenothiazinium salt, a benzophenothiazinium salt, a halogenated xanthene, a squaraine, toluidine blue O, pp 9004, EtNBS, rose bengal, ASQI, a BODIPY (such as zinc(II) dipicolylamine di-iodoBODIPY or BIMPy-BODIPY), a transition metal co-ordination compound, and combinations thereof.
13 . The method of claim 10 , wherein the one or more additives comprises a targeting agent optionally wherein the targeting agent is a cancer targeting agent; optionally wherein the cancer targeting agent is selected from the group consisting of an RGD including cRGD, IRGD, and F3; and NGR peptides and INGR.
14 . The method of claim 10 , wherein the one or more additives comprises a targeting agent optionally wherein the targeting agent is a cardiac targeting agent; optionally wherein the cardiac targeting agent is selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 48.
15 . The method of claim 10 , wherein the one or more additives comprises a photosensitizer agent which is phthalocyanine dye, optionally wherein the phthalocyanine dye is IR700.
16 . The method of claim 9 , wherein at least one arm of the multi-armed PEG is free of the one or more additives.
17 . The method of claim 1 , wherein each of the nanoconstructs has an average diameter of less than about 50 nm.
18 . The method of claim 10 , wherein the one or more additives comprises a targeting agent which is a tumor targeting agent; and wherein the method further comprises, following (b):
(c) providing data identifying the shape, structure, and/or position of a tumor in the subject.
19 . The method of claim 10 , comprising:
(c), following (b), providing data on the concentration of the nanoconstructs and the one or more additives associated to the multi-armed PEG in the subject.
20 . The method of claim 1 , wherein (b) comprises applying one or more fat saturation techniques.