The purpose of this research study is to assess the effects of ZD4054 on prostate cancer that has spread to the bones by using new imaging techniques. In particular, this study will use fluorodeoxyglucose (FDG) and 18F-Sodium Fluoride (NaF) PET/computed tomography (CT) and MRI scans to look for changes in bone metastasis after ZD4054 therapy.

Inclusion Criteria:

1. Men > 18 years of age.
2. Histologically proven adenocarcinoma of the prostate.
3. Presence of radiographic bone metastasis with at least one which is amenable to serial imaging using MRI/PET imaging.
4. Patients must have evidence of progressive disease by either radiographic progression or a rising PSA within 4 weeks prior to registration.
5. Patients must have had prior treatment with bilateral orchiectomy or other primary androgen-deprivation therapy.
6. For patients previously treated with flutamide (Eulexin), Nilutamide (Nilandron), or bicalutamide (Casodex): Patients must have discontinued flutamide > 4 weeks prior to registration with continued evidence of progressive disease. For bicalutamide or nilutamide, patients must have discontinued the drug > 6 weeks prior to registration with evidence of progressive disease.
7. Prior therapy is permitted as long as it was given > 4 weeks prior to registration, and evidence for disease progression is met.
8. Patients must not have had prior radiotherapy < 4 weeks prior to registration.
9. Prior use of bisphosphonates allowed only if started at least 12 or more weeks prior to registration (can continue current dose/schedule while on study).
10. Patient cannot have had prior Strontium 89, Samarium 153, or other radioisotope.
11. No concurrent use of estrogen, or estrogen-like agents
12. Patients must have adequate organ function
13. ECOG performance status 0-2.

Exclusion Criteria:

1. Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine and phenobarbitone, St. John's Wort) within 2 weeks prior to start of study treatment.
2. Prior therapy with endothelin receptor antagonists or family history of hypersensitivity to endothelin antagonists.
3. History of past or current epilepsy, epilepsy syndrome, or other seizure disorder.
4. Stage II, III or IV cardiac failure (classified according to New York Heart Association (NYHA) classification), myocardial infarction within 6 months prior to study entry, or have left ventricular function (LVEF) below the institutional normal limit.
5. QT interval corrected for heart rate (by Bazett's correction) (QTcB) >470 msec.
6. Previous history or presence of another cancer, other than prostate cancer or treated squamous/basal cell carcinoma of the skin, within the last 5 years.
7. Major surgery within 6 weeks of registration.
8. Hemoglobin (Hb) <9 g/dL. Concomitant use of erythropoietin or blood transfusions is allowed.
9. Inability to take or absorb oral medications.

14 months