Phospholipid analogs as diapeutic agents and methods thereof
Inventors
Weichert, Jamey P. • LONGINO, Marc • PINCHUK, Anatoly
Assignees
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Publication Number
US-9550002-B2
Publication Date
2017-01-24
Expiration Date
Abstract
The present invention provides methods and uses of phospholipid ether analogs as diagnostic and therapeutic agents for numerous cancers.
Core Innovation
The invention relates to phospholipid ether (PLE) analogs for cancer imaging and cancer treatment/therapy, including radioiodinated NM404/NM324-like agents. A representative molecular scaffold described is 18-(p-iodophenyl)octadecyl phosphocholine and related phosphocholine analogs, with iodine-radioisotope labeling options including 122I, 123I, 124I, 125I and 131I. The described approach uses radioiodinated phosphocholine compounds to localize in tumors and support cancer diagnosis and treatment.
A problem addressed is the need for improved tumor selectivity compared with non-selective agents and agents associated with inflammatory or low-selectivity uptake, exemplified by FDG. The document attributes tumor-selective localization to a hypothesis involving reduced metabolic breakdown and differential clearance, leading to higher analog retention in tumor tissue than in surrounding normal tissue. Mechanistic association is discussed in terms of reduced PLD activity and/or PLD mRNA, and discrimination between malignant neoplasia versus adenoma/hyperplasia is discussed.
The document discusses that radioiodinated 18-(p-iodophenyl)octadecyl phosphocholine, including 131I-labeled and other iodine-labeled examples, can be used for cancer detection by imaging with retained signal in tumors. It also presents the therapeutic matching concept, in which the same or related radiolabeled phosphocholine agent may be used for therapy with an iodine isotope (e.g., 131I). Supporting observations across multiple cancer types are described as including tumor localization and selectivity in settings such as lung/NSCLC, colorectal/liver, glioma, hepatocellular carcinoma, prostate, breast and lymph node metastasis, and other cancers.
Claims Coverage
The document provides two independent treatment-method claims covering radiolabeled 18-(p-iodophenyl)octadecyl phosphocholine for treating a previously diagnosed cancer in a subject. The inventive features focus on the radiolabeled phosphocholine compound (125I or 131I labeling) and its use as an effective treatment amount, optionally supported by dependent-claim conditions such as selective uptake by cancer cells.
125I-labeled 18-(p-iodophenyl)octadecyl phosphocholine for treating previously diagnosed cancer
Administering to a subject previously diagnosed with cancer an effective amount of 125I-labeled 18-(p-iodophenyl)octadecyl phosphocholine or a salt thereof for treating the cancer.
131I-labeled 18-(p-iodophenyl)octadecyl phosphocholine for treating previously diagnosed cancer
Administering to a subject previously diagnosed with cancer an effective amount of 131I-labeled 18-(p-iodophenyl)octadecyl phosphocholine or a salt thereof for treating the cancer.
Across the independent claims, the main coverage is a cancer treatment method using an effective amount of an iodine-radioisotope-labeled 18-(p-iodophenyl)octadecyl phosphocholine compound (125I in one claim; 131I in the other), with dependent claims further refining treated cancer types and including a premise of selective uptake by cancer cells.
Stated Advantages
Tumor selectivity versus non-selective agents such as FDG is stated as an advantage.
Prolonged retention in tumor tissue compared with surrounding tissue is stated as an advantage.
Reduced inflammatory uptake is stated as an advantage compared with FDG.
The document discusses shipping and half-life considerations in relation to iodine-labeled agents as an advantage.
Documented Applications
Cancer detection/localization by imaging based on higher analog retention in tumors than in surrounding tissue, including 131I-labeled 18-(p-iodophenyl)octadecyl phosphocholine.
Cancer treatment/therapy using iodine-labeled phosphocholine compounds, including therapeutic matching with 131I.
Cancer-type application contexts described include lung/NSCLC, colorectal/liver, glioma, hepatocellular carcinoma, prostate, breast and lymph node metastasis, and additional cancer types discussed in the document.
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