68Ga-Dotatoc Positron Emission Tomography (PET) for Somatostatin Receptor-Positive Neuroendocrine Tumors (NETs)

Rationale and overall study design This study is planned to demonstrate the safety and
efficacy of [68Ga]-DOTA-tyr3-Octreotide ([68Ga]-DOTATOC) as an accurate imaging technique
for diagnosis, staging, and monitoring of response to treatment in patients with
Somatostatin receptor expressing tumors who undergo imaging with a clinical indication.

Neuroendocrine tumors (NET) are rare neoplasms of neuroendocrine origin. Neuroendocrine
tumors are solid malignant tumors that arise from dispersed neuroendocrine cells found
throughout the body. They are well known for their heterogeneity which makes it difficult to
obtain uniform clinical data and establish universal guidelines for the diagnosis and
treatment of NETs. NETs are characterized by overexpression of somatostatin receptors, which
can be visualized and targeted by radiolabeled somatostatin analogues.
111In-diethylenetriaminepentaacetic acid-octreotide scintigraphy (111In-Octreotide) with
single photon emission tomography (SPECT) is currently the standard imaging modality for
evaluating patients with NETs. 111In Octreotide is the only FDA approved radiopharmaceutical
available on the market for assessing the extent of involvement by NETs at both staging and
follow up periods. However, the sensitivity of this imaging modality is lower compared to
the positron emission tomography (PET) radiotracer 68Ga-DOTA0-Tyr3]octreotide
(68Ga-DOTA-TOC). Based on the improved sensitivity, 68Ga DOTATOC PET leads to significant
changes in 30% of patients. Importantly, the radiation exposure of 68Ga-DOTATOC PET is lower
than that of 111In Octreotide and also the imaging with 68Ga-DOTATOC PET scan yields fast
read-outs on the same day compared to 24-48 hour read-outs with 111In Octreotide scan. These
advantages make the 68Ga labeled somatostatin analog more attractive from both the patient
and management perspectives. The improved resolution and quantitation of uptake obtained
with Ga-68 DOTATOC PET should provide a more accurate assessment of somatostatin receptor
density, which will lead to a more accurate prediction of treatment response to somatostatin
analogues.

While the investment costs for the scanner, the radiochemistry equipment are higher for
68Ga-DOTATOC PET/CT compared with 111In-DTPA-octreotide scintigraphy and SPECT, with the
provision of this imaging molecule by an established commercial radiopharmaceutical company
that in with compliance to FDA 21 CFR Part 212 IBA Molecular Inc, NJ, USA, this will not
pose a limitation for the Mount Sinai Medical Center. In this setting, 68Ga-DOTATOC PET/CT
production and personnel costs will be borne by the commercial entity, however, Mount Sinai
Medical Center will purchase the 68Ga-DOTATOC based on a per patient schedule. Since this
imaging modality does not have a quote for reimbursement by the insurance carriers, the
imaging cost is considered a potential burden on the patient until it is approved by the
U.S. Food and Drug Administration (FDA). There is significant amount of European based
clinical data (>1000 patients) to prove the safety and efficacy of this imaging agent,
therefore, a phase II or III clinical trial in the US is redundant and will only delay the
approval of this imaging probe. Recently, Ga-68 DOTATOC has been designated as an orphan
drug by the FDA for the management of NET. This designation will probably lead to faster
approval of the agent, which would greatly benefit NET patients in the US. Currently, there
are only several small U.S.-based clinical trials for Ga-68 labeled NET PET agents available
for patients; otherwise they must travel out of the country if the scan is required to
manage their disease.

The investigators, therefore, aim to provide this superior imaging technique to NET patients
for better disease management by the referring physicians, however, this objective cannot be
attained unless at least a partial funding mechanism exists to make it affordable by the
patients until the approval of this superior imaging probe. In this regard, the
investigators are aiming at recovering the cost of the radiotracer from the local insurance
carrier through the cost recovery system.

Participant Enrollment Participants will be recruited from the Mount Sinai Medical Center.
Participants who will be approached regarding the study are those individuals who are being
seen for known or suspected malignancies.

Patients may remain on their somatostatin therapies throughout the study with no management
change merely based on the 68Ga -DOTATOC PET/CT imaging findings. The management of these
patients will be based on the standard of care and any change will be at the discretion of
the referring physician. All pertinent dosing information must be collected and reported.

Inclusion Criteria:

- Known or suspected somatostatin receptor positive NETs (e.g. carcinoid, pancreatic
neuroendocrine tumors, and pheochromocytoma). Supporting evidence may include MRI,
CT, biochemical markers, and or pathology report.

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

- Off Sandostatin (octreotide acetate)-long acting release (LAR) > 4 weeks and off
immediate release (subcutaneous) for at least 12 hrs prior to 68Ga-DOTATOC PET-CT
imaging

- Able to provide informed consent

- At least 18 years of age

Exclusion Criteria:

- Pregnancy or breast feeding. A negative serum pregnancy test is required for all
female subjects with child- bearing potential

- Surgical resection, chemotherapy, radiation therapy, or biologic therapy since last
Octreoscan + CT; continuation of the same dose of Sandostatin-LAR or subcutaneous
Sandostatin is allowed

- Medical condition uncontrolled by treatment making completion of study unlikely

- Patients exceeding the weight limitations of the scanner or are not able to enter the
bore of the PET/CT scanner due to Body Mass Index (BMI)

- Inability to complete the needed investigational and standard-of-care imaging
examinations due to other reasons (e.g. severe claustrophobia)

- Any additional medical condition, serious intercurrent illness or other extenuating
circumstance that, in the opinion of the Investigator, may significantly interfere
with study performance or interpretation