68Ga-PSMA-PET/CT imaging for locally advanced, recurrent and metastatic adenoid cystic carcinoma or salivary duct carcinoma

PSMA is a transmembrane protein and PSMA expression can be visualized and
quantified by immunohistochemical staining of tissue biopsies with anti-PSMA
monoclonal antibodies. This has been done for many healthy and malignant
tissues. PSMA expression appears to be restricted to a few healthy tissues,
such as the prostate, duodenum, proximal renal tubules, breast and skeletal
muscle.2 Results on PSMA expression of healthy salivary gland tissue are
conflicting. In malignant tissue, PSMA expression was found in prostate cancer
cells and the neovasculature of many other solid malignancies, including renal
cell carcinoma, bladder cancer, colon cancer, neuroendocrine carcinoma,
melanoma, pancreatic cancer, non-small cell lung cancer, breast cancer and
others. In ACC, a study in 54 patients showed PSMA expression in 85% of
patients, and in 70% of patients with recurrent ACC. In SDC, PSMA expression is
currently under study, and the first results show PSMA expression in more than
80% of patients.

Prostate cancer lesions can be targeted efficiently with radiolabeled PSMA
ligands. Labeled with 68Ga, PSMA ligands can be used to sensitively detect
these tumors noninvasively with PET. Labeled with *-emitting radionuclides such
as 177Lu, PSMA ligands are a new class of powerful therapeutics for targeted
radionuclide therapy.

In the current study, we will evaluate the uptake of 68Ga-PSMA by performing
68Ga-PSMA-PET/CT scans in locally advanced, recurrent and metastatic ACC or SDC
patients. If the uptake is high, this forms the rationale for a therapeutic
study with 177Lu-PSMA.

Primary objective
- To evaluate the uptake of 68Ga-PSMA in locally advanced, recurrent and
metastatic ACC or SDC by performing 68Ga-PSMA-PET/CT scans.

Secondary objectives
- To calculate the SUV tumor-to-background ratio and tumor-to-*healthy salivary
gland tissue* ratio.
- Correlate the tumor uptake (SUV) to the degree of immunohistochemical PSMA
expression of the primary tumor on archival tissue or a fresh biopsy.
- To establish whether new metastatic lesions are found by 68GA-PSMA-PET/CT
imaging.

Diagnostic study

Study procedure
1. Before screening visit:
- Eligible patients will be informed about the study during normal patient
care. If the patient is considering to participate, a screening visit will be
planned.
2. Screening visit:
- Review of inclusion and exclusion criteria.
- Obtain written informed consent.
- Review of demographic data, medical history, allergies, and vital signs.
- Asses serum AST, ALT, and creatinine unless done within 14 days prior to
visit.
3. Study visit:
- Perform a 68Ga-PSMA-PET/CT scan according to standard protocol. 68Ga-PSMA
will be administered in a single intravenous dose of 2 MBq/kg in order to
obtain images with PET/CT.
4. Additional analysis: determination of the immunohistochemical PSMA
expression on the most recent tissue material. The patient gives consent for
this analysis, but doe'sn't have to undergo additional procedures.

A patient who decides to participate in this study will need to make 2 extra
visits to the Radboudumc. During the first visit an informed consent will be
signed and the background variables will be taken. During the second visit the
68Ga-PSMA-PET/CT scan will be made. These two visits will take approximately 3
hours in total. The participant is not expected to have complaints from these
procedures and the risks are minimal. The participant will not benefit from
participating in the study. If this study is successful we will pursue a
therapeutic study with 177Lu-PSMA from which the participant may benefit.