Intra-arterial injection of 18F-DCFPyL for the evaluation of Prostate Cancer with Complete Temporary Embolization

For patients with local, advanced, or recurrent PCa, there is a great need for
the development and implementation of improved imaging modalities that can help
to identify the location of the primary PCa tumor in the prostate, and location
of local-regional disease or distant spread with minimal toxicity.
A peptide small molecule which specifically targets Prostate-Specific Membrane
Antigen (PSMA) trans-membrane antigen which is upregulated on PCa cells has
been developed and used clinically for accurate whole body positron emission
tomography (PET) imaging. The systemic administration of this PSMA targeting
agent has yielded tremendous clinical success in both imaging and treating PCa
due to its high tumor sensitivity and rapid pharmacokinetic elimination.
However, one limitation is in visualizing primary tumors in the prostate due to
an inadequate tumor to background ratio.
From experience with the minimally invasive transcatheter treatment of liver
tumors, we know that chemotherapy or radiation can be concentrated within a
tumor via directed intra-arterial administration. This technique isolates the
tumor from the systemic circulation, resulting in the concentration of
therapeutic treatment with minimal to no risk of adverse events related to
nontarget administration. It is hypothesized a similar procedure can be
successfully utilized in the prostate for both imaging and treatment whereby a
PSMA targeting radiopharmaceutical is directly delivered in an intra-arterial
fashion with vascular embolization.

Primary Objective:

* To evaluate the ability to concentrate the radiotracer within the prostate
gland improving the evaluation of the primary prostate tumor.

Secondary Objective(s):

* To evaluate the PET/CT imaging characteristics of transcatheter, prostatic
artery administered 18F-DCFPyL after complete temporary* vascular isolation of
the prostate from the systemic vascularity.

* Assess the leak rate and systemic radiation dose when a PSMA PET tracer is
delivered into the arterial circulation after temporary vascular isolation of
the prostate from the systemic vascularity.

* To calculate the dosimetry of a directly arterially administered PET PSMA for
both the systemic circulation (whole body, liver, spleen, kidneys, and bladder)
and prostate gland after temporary vascular isolation of the prostate from the
systemic vascularity

* To evaluate the changes to the prostate vascularity after temporary prostate
artery embolization.

This is a proof of concept study of the direct intra-arterial administration
via the prostate artery of an imaging tracer as a means to improve clinical
imaging and act as a segregate for dosimetry prior to intra-arterial therapy.
The systemic, intravenous administration of this radiotracer is a standard part
of the normal clinical evaluation of patients with prostate cancer. The study
will be conducted at the Netherlands Cancer Institute (NKI), Amsterdam, The
Netherlands. Duration of inclusion is estimated at 24 months to include the
sufficient number of patients.

The two arms in this project are:
1) Local artery injection of the imaging tracer with no additional embolization
2) Temporary, complete prostate artery embolization (CPAE) with a bioresorbable
particle for temporary blockade of vascular flow

Between 3-5 patients will be recruited for inclusion into each one of the two
groups with potential maximum 10 patients included in the study.

For the purpose of this study a catheter directed angiography of the prostate
arteries will be performed and either CPAE with 50 um resorbable particle or
direct arterial administration of radiotracer will be performed. Embolization
group will subsequently be administered an intra-arterial (i.a.) injection of
18F-DCFPyL into the prostate artery. The second group is comprised of only
direct arterial administration. After angiography a PET/CT and MRI will be
made. Blood samples to evaluate the systemic radiation dose after
administration will be obtained to identify prostate uptake and systemic
nontarget radiation dose.
All included patients will continue be treated with standard of care therapy
for PCa before, during, and after participation without any interruption of
treatment

The patient will undergo an additional minimally invasive procedure consisting
of an angiogram of the pelvis and prostate, this procedure uses radiation for
imaging. The embolization is not permanent. The temporary embolization group
will have the particles reabsorbed after 2 hours. No change in the available
treatments or side effects related to the embolization are expected. The risks
of this procedure are small and include damage to a vessel, bleeding,
infection, kidney injury, and anaphylaxis, however these complications are
extremely rare (e.g. less than 1-2%).
18F-DCFPyL PSMA PET is a commonly employed clinical radiotracer with an
excellent safety profile and low radiation dose. The potential radiation dose
that will be encounter by the prostate with complete absorption of the entire
radiotracer dose within the prostate is safe and negligible, in this extreme
case the radiation dose will have no effect on the prostate or surrounding
pelvic organs.
Three additional blood draws will be required from the patients, the first will
be via the indwelling vascular sheath immediately after infusion. Repeat blood
draws will be obtained at one and two hours after the infusion.
After the procedure the patient will receive a PET/CT scan and a
multi-parametric MRI. This is an out-patient procedure but the patient can
elect to remain in the hospital overnight for observation.
Follow-up will be performed at the patients normal oncologic clinic appointment
and requires no extra visits.

Systemic Intravenous administration of a PSMA PET tracer for prostate
malignancies is an effective and safe imaging treatment, however, limitations
exists in identifying the location of the primary cancer within the prostate
gland due to a low tumor to background ratio and non-target uptake in adjacent
organs such as the bladder. We hope to optimize the first-pass binding in PSMA
positive tumors and limit systemic administration of radiotracer; thus
decreasing the systemic dose and improving the imaging quality and clinical
information that can be obtained from a PSMA PET/CT.
Potential benefits: Systemic Intravenous administration of a PSMA PET tracer
for prostate malignancies is an effective and safe imaging treatment, however,
limitations exists in identifying the location of the primary cancer within the
prostate gland due to a low tumor to background ratio and nontarget uptake in
adjacent organs such as the bladder. We hope to optimize the first-pass binding
in PSMA positive tumors and limit systemic administration of radiotracer; thus
decreasing the systemic dose and improving the imaging quality and clinical
information that can be obtained from a PSMA PET/CT.