Imaging and selective retention of phospholipid ether analogs
The present invention generally relates to imaging and selective retention of phospholipid ether analogs in various neoplastic tissues. Specifically, the present invention relates to imaging and methods for selective retention of analogs, for example, NM404, in cancers such as Colorectal Cancer.
1. A method of detecting neoplasia in a tissue sample from a patient having a phospholipase D (PLD) comprising the step of:
quantifying the PLD protein activity level or the PLD mRNA level in the tissue sample; and
determining whether the tissue sample has a lower level of protein activity than control or surrounding tissue region(s) wherein a lower activity region indicates detection and location of the neoplasia, or
determining whether the tissue sample has a lower level of mRNA than control or surrounding tissue region(s) wherein a lower mRNA level region indicates detection and location of the neoplasia.
2. The method of detecting neoplasia of claim 1 , wherein the PLD mRNA level is quantified by quantitative PCR (QPCR).
3. The method of detecting neoplasia of claim 1 , wherein the patient having the lowered PLD protein activity level or the PLD mRNA is further administered with a phospholipid ether (PLE) analog selected from:
where X is selected from the group consisting of radioactive isotopes of halogen; n is an integer between 8 and 30; and Y is selected from the group comprising NH 2 , N(R) 2 and N(R) 3 , wherein R is an alkyl or arylalkyl substituent or
where X is a radioactive isotope of halogen; n is an integer between 8 and 30; Y is selected from the group consisting of H, OH, COOH, COOR and OR, and Z is selected from the group consisting of NH 2 , N(R) 2 and N(R) 3 , wherein R is an alkyl or arylalkyl substituent,
whereby the administration of the PLE analog in the patient results in the treatment or reduction of said neoplasia in the patient.
4. The method of claim 3 , wherein X is selected from the group of radioactive halogen isotopes consisting of 76 Br, 77 Br, 123 I, 124 I, 125 I, 131 I and 211 At.
5. The method of claim 3 , wherein the phospholipid ether is 18-(p-Iodophenyl)octadecyl phosphocholine, 1-O-[18-(p-Iodophenyl)octadecyl]-1,3-propanediol-3-phosphocholine, or 1-O-[18-(p-Iodophenyl)octadecyl]-2-O-methyl-rac-glycero-3-phosphocholine, wherein iodine is in the form of a radioactive isotope.
6. The method of claim 3 , wherein the PLE analog administered to the patient is further detected by PET, CT, MRI scanning methods and combination thereof.
7. The method of claim 1 , wherein the tissue having the PLD is isolated with laser capture microdissection prior to quantifying the PLD protein level activity or the PLD mRNA activity.
8. The method of claim 1 , wherein average ratio of PLD mRNA level in the control or the normal surrounding tissue to the neoplastic tissue is about 1.1 to about 3000.
9. The method of claim 1 , wherein the neoplasia is 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, Pancreatic cancer and Carcinosarcoma.