Biodistribution/Reproducibility Ga-68 PSMA-HBED-CC

Prostate cancer (PCa) represents the most common noncutaneous cancer and second most common
cause of cancer related death among men in the United States and worldwide. Individual PCa
tumor behavior is variable. Some tumors show slow indolent growth patterns and may never
become clinically significant while others are aggressive and lead to metastases and death.
PCa most commonly metastasizes to bone and lymph nodes. Lungs, liver, and adrenal glands are
less frequent metastatic sites.

Accurate staging and risk stratification is essential to optimal management. Pelvic lymph
node dissection (PLND) which is performed along with radical prostatectomy is the gold
standard for detection of occult nodal metastases but is invasive and has associated
morbidity. PLND offers an additional therapeutic benefit in some patients, but is also
associated with potential complications and can still underestimate the extent of nodal
metastases as 40-50% fall outside the traditional dissection zones [6]. Furthermore, fewer
patients are presenting with nodal metastases at initial presentation due to stage migration,
so more PLNDs need to be performed to benefit one patient. Therefore there is a clear need
for noninvasive imaging options to assist with early and accurate detection of nodal
metastases.

68Ga PSMA-HBED-CC is a urea-based small molecular inhibitor that targets an enzymatic site on
the extracellular domain of the PSMA membrane protein. Based on strong preclinical evidence,
a number of clinical studies of 68Ga PSMA-HBED-CC PET/CT have been performed. Afshar-Oromieh
et al. showed detection of lesions suspicious for PCa metastases in 84% of a cohort of
patients (n=37) being investigated for biochemical relapse, clarification of suspicious
findings on other modalities, or evaluation for possible 131I PSMA ligands. In a larger
retrospective study (n=319) Afshar-Oromieh et al. showed that 68Ga PSMA-HBED-CC PET/CT
detected PCa in 83% of patients with suspected recurrence. In another study Afshar-Oromieh et
al compared 68Ga PSMA-HBED-CC PET/CT to 18F fluoromethylcholine (FCH) PET/CT. At least one
PCa lesion was detected in 87% of patients with 68Ga PSMA-HBED-CC versus 70% of patients with
18F FCH. Among patients in whom PSA values were <2.82 ng/ml at least one lesion could be
detected in 69% of patients with 68Ga PSMA-HBED-CC and 44% patients with 18F FCH.
Tumor-to-background ratios were higher for 68Ga PSMA-HBED-CC. In the aforementioned studies
by Afshar-Oromieh et al. 49 patients with positive scans were further evaluated by biopsy or
surgery and were confirmed as PCa with no false positives. Morigi et al. also showed the
superiority of 68Ga PSMA-HBED-CC over 18F FCH in PET/CT. Detection rates 68Ga
PSMA-HBED-CCPET/CT in multiple studies are higher than for rates reported in the literature
for 11C Choline, 18F Choline, and 11C Acetate [20]. Most importantly the detection rates 68Ga
PSMA-HBED-CCPET/CT in patients with low PSA (<0.5 ng/ml) are more favorable.

Thus preclinical and clinical studies show that 68Ga PSMA-HBED-CC PET/CT is a promising
radiotracer for the early detection of metastatic or recurrent PCa even with low serum PSA
levels.

There will be no control group. For the study group the following inclusion and exclusion
criteria will be followed.

INCLUSION CRITERIA

- Male

- Aged ≥ 18 years

- Histological diagnosis of adenocarcinoma of the prostate OR have a clinical diagnosis
of prostate cancer and on active therapy or have received treatment for prostate
cancer.

- Multifocal metastatic disease in either castrate sensitive or castrate resistant
patients.

- May or may not be on hormonal therapy, chemotherapy, or radium therapy.

- If on hormonal therapy or chemotherapy, must be on it for at least 3 months.

- No plans to undergo prostate cancer therapy administration (with hormone therapy,
chemotherapy, radium therapy, external radiation) between the two study exams.

- At least 2 metastatic soft tissue or bone lesions identified on conventional imaging
(CT, MRI or bone scan).

- Karnofsky performance status of ≥ 50 (or ECOG/WHO equivalent)

- Ability to understand and willingness to sign a consent document.

EXCLUSION CRITERIA

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection requiring hospitalization, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements

- Physical limitation that would limit compliance with the study requirements

- Current enrollment in a therapeutic clinical trial