18F-Prostate Specific Membrane Antigen PET-CT as a potential novel imaging modality for pancreatic cancer: A pilot study (PANSCAN-2)

Theoretical and empirical background of the project proposal:
- In the Netherlands, PC has an incidence of 3.000 new cases per year and is
associated with a dismal prognosis.2 This is mainly due to difficulty in early
detection of the disease. Staging, and hence rational use of treatment, is
highly dependent on information yielded from conventional imaging modalities
(e.g., CT, MRI, EUS). However, almost 50% of surgery is without patient benefit
(e.g., due to benign diagnoses, undetected metastases, or recurrence <6
months), indicating that these imaging modalities are lacking diagnostic
precision and response evaluation accuracy. In surgery for PC, 10% show
metastases at laparoscopy and approximately half of the patients undergoing a
resection will have microscopically positive resection margins (R1), of whom
25% will develop disease recurrence within six months after surgery.
Furthermore, the imaging in patients with locally advanced PC who started
chemotherapy is unreliable.3
Also, 18F-FDG PET-CT has no place in standard health care, mainly due to the
large number of false positive findings, resulting in futile resections of the
pancreas. 18F-FDG PET-CT is therefore only reserved on indication for the
individual patient.3
- Molecular imaging with 18F-PSMA PET may be a promising diagnostic alternative
(figure 1). PSMA is a type II transmembrane glycoprotein highly expressed on
the surface of prostatic cancer epithelial cells. The expression of PSMA in
tumour-associated (neo)vasculature of prostate cancer, breast cancer and
primary gliomas has been reported, and is proven to be also high in PC.5,6
- 18F-PSMA PET has been recently technically validated and successfully
implemented in clinical practice for prostate cancer at Amsterdam UMC, VUmc.7
Radiolabelled PSMA PET-CT has proven highly successful for primary staging and
restaging of prostate cancer patients and is currently being implemented
worldwide.8
- Recently, it has been shown that PSMA is also expressed on the endothelium of
tumour-associated neovasculature in PC tissue, in 63-84% of the investigated
samples. 5,6 Immunohistochemical experiments from our group showed an
acceptable high expression of PSMA in 4 out 5 patients with PC de novo, as well
as in 32 out 33 PC patients after neoadjuvant treatment (mean tumor H-score of
99 (maximum 300)), comparable with the reported results in the literature.
These experiments also showed no expression on adjacent normal and pancreatitis
tissue (H-score 0), thus yielding high contrast (figures 2 and 3).

To investigate the feasibility of using 18F-PSMA PET-CT as a tumor-specific
molecular imaging in PC, thus allowing for improved detection, therapy
selection, and therapy response assessment.

The PANSCAN-2 study will be a non-blinded, two locations (Amsterdam UMC) pilot
study.

The study intervention comprises one 18F-PSMA PET-CT scan prior to treatment
initiation.

The burden of study participation is low. Patients will undergo one extra
18F-PSMA PET/low-dose CT (for attenuation and anatomical correlation),
additional to all standard imaging modalities prior to pancreatic surgery (e.g.
diagnostic CT thorax/ abdomen). The only additional risk of this scan for
patients is the intravenous access cannula followed by administration of
18F-PSMA; which could give a local hematoma, run subcutaneously or give an
allergic reaction.