Systems and methods for minimally-invasive assessment of toxicity-induced tissue injury

Patent metadata

Field	Value
Publication number	US-11607462-B2
Application number	US-201815981568-A
Country	US
Kind code	B2
Filing date	May 16, 2018
Priority date	May 16, 2017
Publication date	Mar 21, 2023
Grant date	Mar 21, 2023

Abstract

Provided herein are compositions, systems, and methods for minimally-invasive assessment of toxicity-induced tissue injury. In particular, external (e.g., whole-body) scanning is employed to detect toxicity-induced injuries, such as those caused by chemotherapeutics.

First claim

The invention claimed is:

1. A method of detecting toxicity-induced injury through generating a whole body visual map of systemic toxicity-induced injury in intact organs and tissues of a subject by whole body in vivo imaging, the method comprising:
(a) administering to the subject for a period of time a toxicity-inducing chemical, followed by administering a molecular imaging agent to the subject, wherein the molecular imaging agent comprises a detectable moiety selected from technetium-99m ( 99m Tc), gallium-67 ( 67 Ga), yttrium-91 ( 91 Y), indium-111 ( 111 In), rhenium-186 ( 186 Re), thallium-201 ( 201 Tl), gadolinium(III), iron oxide, iron platinum, or manganese directly bound to a binding moiety specific for an externalized phospholipid selected from duramycin, duramycin B, duramycin C, cinnamycin, or a PE-binding portion thereof;
(b) performing molecular imaging scans at multiple time points of the subject;
(c) detecting the molecular imaging agent within the subject dynamically by determination of changes in signal intensity, spatiotemporal occurrence of signal distribution or signal changes over time,
wherein the combination of the agent and the scanning methods minimizes systemic background, improves target-to-background ratio so that high-intensity as well as low diffusive signals are dynamically detected over an effective linear range,
wherein statistically elevated signals are identified in bones, adipose tissue, heart, lung, muscle, skeletal muscles, skin, stomach, colon, kidneys, thymus, liver, spleen, or small intestine tissues,
wherein the signals may appear within eight hours post-treatment or may peak on or after day three post-treatment, and
wherein the measured signal changes create a systemic whole-body visual toxicity profile thereby mapping toxicity-induced injury of the toxicity-inducing chemical.

2. The method of claim 1 , wherein the molecular imaging scan comprises a technique selected from Magnetic Resonance Imaging (MM), planar scintigraphy (PS), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Computed Tomography (CT).

3. The method of claim 1 , wherein the toxicity-inducing chemical is- a chemotherapeutic or other drug that may cause a toxicity-induced tissue injury.

Assignees

• Univ Northwestern

Inventors

• Zhao Ming
• Johnson Steven E

Classifications

• A61K49/06

  Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations · CPC title

• A61K49/0002 Primary

  General or multifunctional contrast agents, e.g. chelated agents · CPC title

• A61K51/08 Primary

  Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins} · CPC title

• A61K2123/00

  Preparations for testing in vivo · CPC title

• A61K51/088

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title