PROSTATE CANCER:

[1] For staging of newly diagnosed patients at high risk for metastases, i.e., those with either: a) a Gleason score * 7 and a prostate-specific antigen (PSA) level * 20 ng/mL, b) a Gleason score of 8-10 or c) a Gleason score * 6 and T3 disease.

[2] For detection of residual and/or recurrent prostate cancer in patients who have undergone primary therapy, prior to selection of an appropriate salvage therapy.

[3] For increasing the accuracy in targeting brachytherapy or external beam irradiation to areas at high risk for recurrent disease. These agents will prove particularly useful in this regard when the imaging studies we perform are fused with pelvic computed tomography (CT) scans obtained on our PET/CT scanner.

[4] For the ligands labeled with I-131 (or other suitable therapeutic radionuclide), radioimmunotherapy initially as salvage and, as more experience is gained, as primary therapy for prostate cancer, particularly micrometastatic disease. Such therapy could also be curative or at least palliative for bony metastatic disease, as PSMA is upregulated in hormone-refractory disease.

GLUTAMATERGIC TRANSMISSION:

Abnormal glutamatergic transmission has been hypothesized for a variety of nervous system disorders. [11C]MCG is a probe of GCP II, an enzyme involved in neuronal glutamate production and regulation. Applications of this probe to glutamatergic transmission include:

[1] Study of alterations in GCP II activity in stroke, Alzheimer’s disease, Parkinson’s disease, schizophrenia and peripheral neuropathy. The goals include early detection and therapeutic monitoring.

[2] Dose titration of patients who are to be treated with drugs that act at GCP II, by performing dose-occupancy studies. This technique is particularly useful in segregating patients into those who may benefit from treatment that affects GCP II from those who would not and for providing the minimum effective dose in order to avoid side-effects. Also, once treatment is began, [11C]MCG and/or its analogs can be used to calculate how much drug is actually binding to GCP II.

TUMOR NEOVASCULATURE:

Antiangiogenic therapies are proliferating, with several in clinical trials. Because GCP II/PSMA is upregulated in neovasculature in a variety of tumors (renal cell, bladder, colon, neuroendocrine, glioblastoma, melanoma, pancreatic, lung, sarcoma and breast), imaging it may provide a marker for the effectiveness of antiangiogenic therapies. Unlike magnetic resonance imaging-based techniques, the nuclear techniques described herein (PET and SPECT) are quantitative. Selection of patients for such therapies could also be performed with these imaging agents.