US 2020/0206369 A1 · IMAGING OF TUMOR-ASSOCIATED MACROPHAGES

Abstract

Presented herein are methods and compositions for non-invasive imaging of TAMs with discoidal high-density lipoproteins to assess prognosis and therapy outcome. TAMs are increasingly investigated in cancer immunology, and are considered a promising target for better and tailored treatment of malignant growths. Although TAMs also have high diagnostic and prognostic value, TAM imaging still remains largely unexplored. Imaging agents/methods provided herein are of value for non-invasive in vivo evaluation of TAM burden, not only in preclinical but also in clinical settings.

Claims11

Dependent claims

A method of imaging tumor-associated macrophages (TAMs) by high density lipoprotein positron emission tomography (HDL PET), the method comprising:

administering to a subject a composition comprising a discoidal high density lipoprotein nanoparticle, the nanoparticle comprising Apolipoprotein 1 (ApoA1) and one or more phospholipids, wherein the nanoparticle is radiolabeled with a radioisotope via incorporation of a chelator-modified ApoA1 with the radioisotope and optionally incorporation of a chelator-modified phospholipid with the radioisotope;
and
detecting the radioisotope via PET after accumulation of the nanoparticle in a region of TAMs.

A method of making a composition comprising a discoidal high density lipoprotein nanoparticle, the nanoparticle comprising Apolipoprotein 1 (ApoA1) and one or more phospholipids, wherein the nanoparticle is radiolabeled with a radioisotope via incorporation of a chelator-modified ApoA1 with the radioisotope and optionally incorporation of a chelator-modified phospholipid with the radioisotope, the method comprising one or more of (i), (ii), (iii) and (iv):

(i) modifying ApoA1 with a chelator, reacting the modified ApoA1 with a radioisotope comprising an oxalate moiety, and incorporating the radiolabeled chelator-modified ApoA1 in the nanoparticle;
(ii) modifying ApoA1 with a chelator, incorporating the chelator-modified ApoA1 in the nanoparticle, and reacting the chelator-modified ApoA1 with a radioisotope comprising an oxalate moiety;
(iii) modifying DSPE with a chelator, reacting the modified DSPE with a radioisotope comprising an oxalate moiety, and incorporating the radiolabeled chelator-modified DSPE (or other phospholipid) in the nanoparticle;
and
(iv) modifying DSPE with a chelator, incorporating the chelator-modified DSPE in the nanoparticle, and reacting the chelator-modified DSPE with a radioisotope comprising an oxalate moiety.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application

16/705,188Filed 5 Dec 2019

Priority

20 Apr 2015

Published

2 Jul 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

A61K 51/0408
Lipids, e.g. triglycerides; Polycationic carriers: phospholipids
A61K 51/1234
Dispersions, suspensions, colloids, emulsions, e.g. perfluorinated emulsion, sols: liposomes
A61P 35/00
Antineoplastic agents
C07B 59/008
Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se: peptides; Proteins

Imaging of tumor-associated macrophages

Life of this patent

Imaging of tumor-associated macrophages

Life of this patent

Abstract

Claims11