Inclusion Criteria:

- Histological diagnosis of prostate cancer

- Evidence of metastatic disease by radiologic criteria

- Bone scan within 4 weeks of starting therapy

- Creatinine within 2 weeks of registration, calculated creatinine clearance >
60ml/min.

- Minimum life expectancy of 6 months

- Willingness to have pre-therapy PET scans performed within 2 weeks after registration
and post therapy PET scan performed within 1 week after dose of Zometa (a total of 3
PET scans required)

- Calculated creatinine clearance > 50ml/min.

- No prior Zoledronate therapy

- Patients must have disease progression despite testosterone suppression
(level<50ng/ml); progression can be by rising PSA ( at least 2 values at least 2
weeks apart) or by new lesions on scans or progression of existing lesions on CT
scan.

- No concomitant systemic therapy for metastatic prostate cancer is allowed except LHRH
analogue should be continued if necessary to maintain testosterone suppression.

- No concomitant radiation therapy

- Prior RT is allowed if completed at least 2 weeks prior to registration.

- Presence of measurable or evaluable disease

- If RT has been administered, disease outside the RT port is required.

- Willingness to sign informed consent.

- Registration and willingness to sign informed consent for separate PET protocol 2335
that describes the PET scan procedure.

- Patients must have good oral hygiene which includes having a recent dental evaluation

Exclusion Criteria:

- Patients who are unable to swallow

- Patients with dental cavities that are likely to need dental extraction or root canal
treatment as management