To determine if stimulated salivation during the biodistribution of PSMA-ligands causes a significant increase in the accumulation in salivary glands
ID
Source
Brief title
Condition
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The accumulation of systemically administered PSMA-ligands in salivary glands
on PET/CT.
Secondary outcome
To screen for potential influence of oral intake on the biodistribution of
PSMA-ligands on PET/CT in other organs and tumour.
Background summary
Many pharmaceuticals can damage salivary glands, and this can lead to a dry
mouth (xerostomia) with detrimental effect on quality of life. Systemically
administered pharmaceuticals reach the salivary glands via blood supply and
diffusion, and their accumulation can be further augmented by active or passive
transporters. This also applies to radiopharmaceuticals used in radionuclide
therapy (RNT). Radiolabelled ligands to the prostate-specific membrane antigen
(PSMA) are increasingly used to treat metastatic prostate cancer. The currently
applied Lutetium-177-PSMA-617 ligand (Lu-PSMA) shows very high uptake in
salivary glands, which is explained by the high perfusion of salivary glands
and the abundant expression of the PSMA receptor on their acinar and ductal
seromucous cells. As a result, salivary glands are inadvertently exposed to
high radiation doses in Lu-PSMA treatment, with xerostomia as a known
dose-limiting factor.
Salivation is stimulated during intake, and this is known to induce an increase
in salivary gland perfusion of up to 10-20x baseline values. It is therefore
possible that salivary gland stimulation during the biodistribution phase of
PSMA-ligands leads to increased delivery and binding in salivary glands. If
this is the case, intake and activation of salivation should be avoided during
the administration and biodistribution of therapeutic doses of Lu-PSMA. This is
currently not advised in clinical protocols, with a potential risk on avoidable
toxicity and reduced quality of life.
The hypothesis is that stimulation of salivation during the biodistribution
phase of PSMA-ligands leads to increased accumulation in salivary glands. The
uptake of PSMA-ligands can be assessed with quantitative PET/CT imaging using
the diagnostic radiopharmaceutical 18Fluor-DCFPyl (F-PSMA) or 68Gallium-PSMA
(Ga-PSMA). The biodistribution of current PSMA-ligands is very fast, a
significant part of administered PSMA-ligand binds its target within the first
10 minutes. Salivation representative for normal intake can be stimulated for
10 minutes by continuous intake, chewing and swallowing of food that contains
sugar, fat and acids. An increase in PSMA-ligand uptake in salivary glands due
to intake will predict a similar unwanted effect for treatment with Lu-PSMA.
Study objective
To determine if stimulated salivation during the biodistribution of
PSMA-ligands causes a significant increase in the accumulation in salivary
glands
Study design
Single center prospective interventional phase II study.
Study burden and risks
Participation in this study has no significant risks. Participation does not
induce a delay in diagnosis or treatment, and imaging results have no impact on
the diagnosis or treatment of the prostate cancer. Patients will receive 1
additional PSMA PET/CT scan, with a total procedure duration of 1,5 hour and an
estimated radiation dose of 6-7 mSv. This dose is well within the range of
normal diagnostic procedures and does not induce a significant risk in this
population with prostate cancer.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
- Received PSMA PET/CT on clinical indication (< 1 month before study scan)
- Salivary glands and lacrimal glands visible in the baseline PSMA PET/CT scan
Exclusion criteria
- Poor quality of the baseline PSMA PET/CT scan
- Planned start or changes in treatment between the baseline scan and study
scan.
- Age <18y
- Inability to provide informed consent
- Diabetes Mellitus
- Vegan diet
- Claustrophobia
- History of disease or treatment involving the salivary glands, like malignant
or benign tumour, sialoadenitis, stone, surgery, SLE, RT to head-neck, etc
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL71902.031.20 |