Phospholipid ether analogs as agents for detecting and locating cancer, and methods thereof
Inventors
Weichert, Jamey P. • LONGINO, Marc • PINCHUK, Anatoly
Assignees
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Publication Number
US-9579406-B2
Publication Date
2017-02-28
Expiration Date
Abstract
The present invention provides methods for treating, detecting and locating recurrence of cancer, radiation and chemo insensitive cancer or metastasis of cancer selected from the group consisting of Lung cancer, Adrenal cancer, Melanoma, Colon cancer, Colorectal cancer, Ovarian cancer, Prostate cancer, Liver cancer, Subcutaneous cancer, Squamous cell cancer, Intestinal cancer, Hepatocellular carcinoma, Retinoblastoma, Cervical cancer, Glioma, Breast cancer and Pancreatic cancer in subject using phospholipid ether analogs.
Core Innovation
The invention provides a method for detecting radiation- and chemo-insensitive cancer or cancer metastasis in a subject using a 124I-labeled phospholipid ether analog, including 124I-labeled 18-(p-iodophenyl)octadecylphosphocholine and 124I-NM404. The subject is administered the tracer, and an organ suspected of having radiation- and chemo-insensitive cancer or cancer metastasis is determined to retain a higher level of the tracer than surrounding regions, where the higher retention region indicates detection by measuring 124I radioactivity in the subject.
The patent links the phospholipid ether analog to phospholipase D activity and PLD mRNA, and states that scarcity of PLD leads to metabolic trapping and sustained tumor retention of the radiolabeled phospholipid ether analog. This retention behavior is described for radiolabeled forms including 125I-NM404, 124I-NM404, and 131I-NM404 and is used as the basis for detecting otherwise radiation- and chemo-insensitive cancer or cancer metastasis.
The document further presents tracer and clinical mass dosing considerations for the radiolabeled NM404 tracer, including toxicology and dosimetry rationale. It includes GLP single-dose toxicology studies in rats and rabbits, preclinical tumor localization and biodistribution, and preliminary preclinical and clinical evaluation including human pharmacokinetics and imaging protocols in NSCLC and prostate cancer.
Claims Coverage
The claim coverage centers on a method for detecting radiation- and chemo-insensitive cancer or cancer metastasis using 124I-labeled 18-(p-iodophenyl)octadecylphosphocholine and determining higher retention in a suspected organ relative to surrounding regions by measuring 124I radioactivity. The independent claim contains two inventive features, with dependent claims refining the measurement modality and adding MRI-based detection of the suspected organ.
Detection by higher retention of 124I-labeled 18-(p-iodophenyl)octadecylphosphocholine
Administer 124I-labeled 18-(p-iodophenyl)octadecylphosphocholine to the subject, and determine whether an organ suspected of having radiation- and chemo-insensitive cancer or cancer metastasis retains a higher level of the 124I-labeled 18-(p-iodophenyl)octadecylphosphocholine than surrounding regions, wherein a higher retention region indicates detection by measuring 124I radioactivity in the subject.
PET for measuring 124I radioactivity with MRI detection
Measure 124I radioactivity using PET scanning and detect the suspected organ by MRI in the subject having an organ suspected of having radiation- and chemo-insensitive cancer or cancer metastasis.
SPECT for measuring 124I radioactivity
Measure 124I radioactivity using SPECT in the method for detecting radiation- and chemo-insensitive cancer or cancer metastasis.
Gamma camera scintigraphy for measuring 124I radioactivity
Measure 124I radioactivity using gamma camera scintigraphy in the method for detecting radiation- and chemo-insensitive cancer or cancer metastasis.
Overall, the claims cover retention-based detection using 124I radioactivity from 18-(p-iodophenyl)octadecylphosphocholine, with dependent claim refinements that constrain the radioactivity measurement modality to PET, SPECT, or gamma camera scintigraphy, and additionally include MRI-based detection of the suspected organ.
Stated Advantages
Less localization in inflammatory/infectious tissue, resulting in reduced background.
Reduced renal bladder activity.
Longer shipping half-life for 124I.
Enhanced imaging compared with a predecessor tracer (NM324).
Documented Applications
Human pharmacokinetics and imaging protocols are described for NSCLC and prostate cancer, including exploratory PET-CT studies with I-124 in metastatic and organ-confined prostate cancer.
Detecting radiation- and chemo-insensitive cancer or cancer metastasis in a subject, including detection of recurrence.
Locating suspected tumor-containing organs by identifying higher tracer retention regions than surrounding tissue.
Imaging-based detection using PET/CT and/or SPECT/gamma camera scintigraphy, and adding MRI to detect the suspected organ.
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