Compositions and methods for diagnosing and monitoring ovarian cancer progression and treatment
The present invention provides compositions and methods useful for diagnosing, monitoring the progression, identifying the location, and monitoring the treatment response in ovarian cancer based on detecting and locating VCAM-1 expression.
1. A method for differentiating platinum-sensitive metastatic ovarian cancer from platinum-resistant metastatic ovarian cancer, said method comprising administering an effective amount of a platinum-based chemotherapeutic agent to a subject with ovarian cancer, determining the level of VCAM-1 expression in said subject following said administration and comparing said VCAM-1 level to the level of VCAM-1 expression in said subject prior to administration of said chemotherapeutic agent or to a standard value of VCAM-1 levels, wherein said VCAM-1 levels in said subject are determined by administering to said subject an effective amount of a VCAM-1 imaging probe that binds to VCAM-1 or contacting a biopsy from said subject with an effective amount of a VCAM-1 imaging probe, and then determining the amount of VCAM-1 levels in said subject or in said biopsy, wherein said VCAM-1 probe is a multimeric peptide ligand complex comprising SEQ ID NO:1, each of said peptides is coupled to polyethylene glycol, said polyethylene glycol is coupled to a chelating agent via a linking agent, and optionally at least one imaging agent is coupled to said chelating agent, wherein a decrease in VCAM-1 levels following said administration is an indication that the ovarian cancer is platinum-sensitive and no change in VCAM-1 levels is an indication that the ovarian cancer is platinum-resistant, thereby differentiating platinum-sensitive metastatic ovarian cancer from platinum-resistant metastatic ovarian cancer.
2. The method of claim 1 , further wherein a cancer treatment regimen is designed and implemented based on whether the subject has a platinum-sensitive or platinum-resistant metastatic ovarian cancer, wherein when said ovarian cancer is platinum-sensitive said subject is treated with platinum-based therapy and when said ovarian cancer is platinum-resistant a non-platinum-based therapy is used to treat said subject.
3. The method of claim 1 , wherein said imaging agent is a radionuclide.
4. The method of claim 3 , wherein said radionuclide is 111 In.
5. The method of claim 1 , wherein said probe has the formula [(VHPKQHRGGSPEG5K)4K]2-KK(DOTA)-βA-NH 2 (tVCAM-4).
6. The method of claim 5 , wherein said probe is 111 In-tVCAM-4.
7. The method of claim 6 , wherein said imaging agent is detected with a single photon emission computed tomography/computed tomography (SPECT/CT) scanner coupled to a computer, and imaging data are collected and analyzed using a program to quantify or compare levels of VCAM-1.
8. The method of claim 7 , further wherein the location of said imaging agent is determined.
9. The method of claim 1 , wherein said platinum-based chemotherapeutic agent is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, satraplatin, picoplatin, nedaplatin, triplatin, and lipoplatin.
10. The method of claim 1 , further comprising the step of diagnosing platinum-sensitive or platinum-resistant ovarian cancer.
11. The method of claim 1 , further comprising reporting the indication of platinum-sensitive or platinum-resistant ovarian cancer to the subject or physician.
12. The method of claim 1 , further wherein the VCAM-1 levels are monitored during treatment by detecting and measuring VCAM-1 levels.
13. The method of claim 1 , further wherein the progression of the ovarian cancer is monitored by detecting and measuring VCAM-1 levels.