This pilot clinical trial studies fludeoxyglucose F18 (FDG)-positron emission tomography (PET) in imaging patients with prostate cancer treated with ranolazine. Diagnostic procedures, such as FDG-PET, may help find prostate cancer and find out how far the disease has spread. Giving ranolazine may enhance FDG-PET imaging by increasing the amount of glucose available for uptake by the scan.

PET scans have traditionally not been very good at detecting prostate cancers. This is because prostate cancer cells do not take up glucose well so the signals are very weak. The ability of PET imaging to detect cancers requires that the cancer cells take up glucose into the cells. Different methods are being tested to see if we can improve the detection of prostate cancers using PET scans.

Ranolazine is a drug that is already approved by the FDA for treatment of chronic chest pain in people with heart disease. Ranolazine has been studied in the laboratories at the University of Colorado Denver, Anschutz Medical Campus. Ranolazine has been added to prostate cancer cells and grown in petri dishes and in animals in the laboratory. It has been shown to increase the glucose uptake of prostate cancer cells. The goal of this study is to see if patients taking ranolazine will have better PET imaging of their prostate cancers.

Inclusion Criteria:

1. Written informed consent has been obtained.
2. Adults over 18 years of age.
3. Histological or cytologically confirmed prostate adenocarcinoma.
4. Arm 1 patients must have treatment-naïve, Gleason ≥ 7 prostate cancer based on transrectal ultrasound (TRUS) biopsy, have localized disease, and have decided to undergo radical prostatectomy (open or robotic) as definitive treatment for their prostate cancer.
5. Arm 2 patients must have lymph node, soft tissue, bone, or visceral metastatic disease measuring ≥ 1 cm (lytic component if bone), documented by either CT or MRI imaging within 6 weeks of signing consent. Arm 2 patients may have hormone-sensitive or castrate-resistant disease and may be receiving treatment with hormonal therapies.
6. For Arm 1 patients, the time from the TRUS prostate biopsy to the planned first study PET scan must be ≥ 1 month. For patients who have undergone prior prostate mapping biopsy, the time from the mapping biopsy to the planned first study PET scan must be ≥ 2 months.
7. For Arm 1 patients, participation in this study, in the opinion of the treating physicians, will not introduce delays in surgery that would adversely affect the patient.
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
9. Fasting blood glucose ≤ 120 mg/dL.
10. Adequate renal function (Creatinine ≤ 1.5 X ULN)
11. Adequate hepatic function (bilirubin < 1.5 X upper limit of normal (ULN), alanine aminotransferase (ALT) < 1.5 X ULN, aspartate aminotransferase (AST) < 1.5 X ULN, and albumin ≥ 3 g/dL. For patients with known bone metastases, alkaline phosphatase < 5 X ULN is acceptable.
12. Must be able to take oral medication without crushing, dissolving or chewing tablets.
13. Written authorization for use and release of health and research study information has been obtained.
14. Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection during the study and for 1 week after the last dose of ranolazine.

Exclusion Criteria:

1. Have small cell carcinoma or neuroendocrine component >50%.

2. Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of ranolazine.

3. Documented hypersensitivity to any component of ranolazine (Ranexa®) pills.

4. Need for medications that are:

   1. strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir),
   2. moderate CYP3A inhibitors (e.g. diltiazem, verapamil, erythromycin, fluconazole, grapefruit juice or grapefruit-containing products),
   3. CYP3A inducers (e.g. rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's wort),
   4. CYP3A substrates with a narrow therapeutic range (e.g. cyclosporine, tacrolimus, sirolimus),
   5. P-gp inhibitors or substrates (e.g. cyclosporine, digoxin),
   6. polypeptide 6 (CYP2D6) substrates (e.g. tricyclic antidepressants and antipsychotics),or
   7. simvastatin at doses > 20 mg/day.

5. Have corrected QT interval (QTc)> 450 msec (male) or > 470 msec (female) on 12-lead electrocardiogram.

6. Poorly controlled diabetes, hemoglobin A1c (Hgb A1C) >9 or random blood glucose >250mg/dL.

7. Active or symptomatic viral hepatitis or chronic liver disease.

8. Clinically significant heart disease as evidenced by:

   1. myocardial infarction, or
   2. arterial thrombotic events in the past 6 months,
   3. severe or unstable angina, or
   4. New York Heart Association Class III-IV heart disease or
   5. cardiac ejection fraction measurement of <50%.

9. Active infection requiring antibiotics.

10. Major surgery or radiation treatment within 3 months.

11. Cytotoxic chemotherapy within 4 weeks.

12. Immunotherapy within 6 months.

13. Any prior therapy with Radium-223, Samarium, or Strontium.

14. Arm 1 patients may not have received any prior luteinizing-hormone-releasing hormone (LHRH) agonists/antagonists, anti-androgens, or chemotherapy for their prostate cancer. 5-alpha reductase inhibitors (finasteride, dutasteride) may be allowed.

15. Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements.