Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000981426
Ethics application status
Approved
Date submitted
13/08/2025
Date registered
5/09/2025
Date last updated
5/09/2025
Date data sharing statement initially provided
5/09/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
18F-Fluorodopa (18F-FDOPA) PET/CT for the localisation of prolactinomas.
Scientific title
18F-FDOPA PET/CT for the localisation and confirmation of functional adenomas in patients with hyperprolactinemia, a prospective case control study.
Secondary ID [1] 315072 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pituitary Adenoma 338533 0
Pituitary Neuroendocrine tumours 338648 0
Condition category
Condition code
Metabolic and Endocrine 334838 334838 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is a single 18F-FDOPA PET/CT (Positron emission tomography/computer tomography) scan, performed by a Nuclear medicine specialist. A single 150MBq dose of radiotracer FDOPA will be administered over 15 seconds with a line flush with 20mL saline. A co-registered, non-contrast, low dose CT will be performed, with the PET acquisition, for anatomical localisation. Scan duration up to 1 hour.

The main cohort is a comparison of prolactinomas and non-functional pituitary adenomas, which is the cross-sectional arm of the study. The intervention group is prolactinomas (microprolactinomas and macroprolactinomas) and the disease control group is non-functional pituitary adenomas.

There will also be an exploratory sub-study which will also have the single intervention of a FDOPA PET/CT (administered as above, by a nuclear medicine specialist). It will include possible occult microprolactinomas defined as persistent serum prolactin greater than or equal to 2-fold normal but nil pituitary adenoma on MRI. This is to determine if FDOPA avidity is present in this patients despite normal MRI scans.

There will also be a prospective arm of the study which will be all patients with a baseline FDOPA PET/CT (including those from the cross sectional and exploratory arms of this study), who then receive dopamine agonist therapy as routine clinical care. Therefore all cross-sectional arm patients who commence on DA therapy will be invited to participate.

The cross sectional, exploratory and prospective arms will then collect prolactin levels and MRI results performed by the treating clinicians in the usual clinical care of prolactinoma and pituitary adenoma patients with MRI scans at 3 and 12 months and serum prolactin at 3-6 months and 12 months. Audit of imaging reports, clinical records and lab results will be performed regularly by the investigators to monitor adherence.
Intervention code [1] 331741 0
Diagnosis / Prognosis
Comparator / control treatment
The control group for this study is unequivocal non-functional pituitary adenomas, which is a disease control group. This includes non-functional pituitary adenomas that are 5 to 9 mm on MRI with a serum prolactin that is normal. For larger non-functional pituitary adenomas (pituitary adenoma greater than or equal to 10mm on MRI), the serum prolactin must be less than or equal to 2-fold normal (to allow for stalk effect).
Control group
Active

Outcomes
Primary outcome [1] 342468 0
The 18-F-FDOPA avidity of the pituitary lesion.
Timepoint [1] 342468 0
At time of scan (one time point, after screen and enrolment).
Secondary outcome [1] 450945 0
Response to dopamine agonist therapy
Timepoint [1] 450945 0
3-6 months and 12 months post FDOPA PET/CT.
Secondary outcome [2] 450946 0
Prolactinoma size
Timepoint [2] 450946 0
MRI at enrolment and repeated at 3-6 months and 12 months post FDOPA PET/CT.
Secondary outcome [3] 451347 0
Positive predictive value of FDOPA PET/CT
Timepoint [3] 451347 0
Compared to baseline prolactin level and MRI at enrolment then follow up MRI and prolactin level 3-6months and 12 months post FDOPA PET/CT.
Secondary outcome [4] 451348 0
Negative predictive value of FDOPA PET/CT
Timepoint [4] 451348 0
Compared to baseline prolactin level and MRI at enrolment then follow up MRI and prolactin level 3-6months and 12 months post FDOPA PET/CT.
Secondary outcome [5] 451349 0
Sensitivity of FDOPA PET/CT
Timepoint [5] 451349 0
Compared to baseline prolactin level and MRI at enrolment then follow up MRI and prolactin level 3-6months and 12 months post FDOPA PET/CT.
Secondary outcome [6] 451350 0
Specificity of FDOPA PET/CT
Timepoint [6] 451350 0
Compared to baseline prolactin level and MRI at enrolment then follow up MRI and prolactin level 3-6months and 12 months post FDOPA PET/CT.
Secondary outcome [7] 451351 0
Accuracy of FDOPA PET/CT
Timepoint [7] 451351 0
Compared to baseline prolactin level and MRI at enrolment then follow up MRI and prolactin level 3-6months and 12 months post FDOPA PET/CT.

Eligibility
Key inclusion criteria
Cross sectional arm criteria:
1) Unequivocal macro prolactinomas (pituitary adenoma greater than or equal to 10mm on MRI + serum prolactin greater than or equal to 10-fold normal)
2) Unequivocal microprolactinomas (pituitary adenoma 5-9mm on MRI + serum prolactin greater than or equal to 4-fold normal)
3) Unequivocal macro NFPAs (pituitary adenoma greater than or equal to 10mm on MRI + serum prolactin less than or equal to 2-fold normal).
4) Unequivocal micro NFPAs (pituitary adenoma 5-9mm on MRI + serum prolactin normal)
Exploratory arm criteria:
Possible occult microprolactinomas defined as persistent serum prolactin greater than or equal to 2-fold normal but nil pituitary adenoma on MRI.
Prospective arm criteria:
All patients with a baseline FDOPA PET/CT (including those from the cross sectional and exploratory arms of this study), who then receive Dopamine Agonist (DA) therapy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to obtain consent;
2. Age 10 half-lives for each drug):
a) Cabergoline within 4 weeks*
b) Bromocriptine within 2 days**
6. Previous radiotherapy with pituitary in the field of therapy;
7. Inability to interrupt confounding medications;
a) DA use for other conditions: Parkinson’s disease, restless leg syndrome
b) Dopamine antagonists:
i) 24 hours for antiemetics: metoclopramide, prochlorperazine, domperidone.
ii) 3 days for Antipsychotics, : Haloperidol, quetiapine, olanzapine, risperidone, paliperidone***
8. Alternative explanation for hyperprolactinemia as determined by an endocrinologist
*Cabergoline, half-life 63 to 109 hours
**Bromocriptine, half-life 3 to 6 hours, although biphasic
***Longer half-life antipsychotics, such as aripiprazole or IM formations, may require longer washout periods to ensure >10 half-lives and will be reviewed individually by the study team.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
The trial includes a cross-sectional arm, a substudy and a prospective cohort. The cross-sectional arm will assess micro and macroprolactinomas against a control group of non-functional pituitary adenomas (Both micro and macroadenomas).
Exploratory sub-study arm will assess patients with a suspected occult microprolactinoma (with elevated prolactin but no pituitary adenoma on MRI).
The prospective cohort will then include all patient who had the FDOPA PET/CT (from the cross-sectional and exploratory arms) and then were commenced on dopamine agonist therapy in routine clinical care and their MRI scan and prolactin levels will be monitored.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Descriptive statistics will be used to describe baseline patient characteristics. Analysis of the correlation between PET metrics and clinical and structural imaging characteristics will be undertaken using statistical software.

A multivariate analysis will be performed on the adenoma size, prolactin level, and PET metrics (PET SUVmax, SUVpeak and SUVmean values). The Pearson correlation coefficient (r) will be calculated assuming a linear relationship. A t test will then be used to ensure the r statistic differs significantly from zero (with p <0.05).

For the categorical data (non-parametric) data (positive vs negative localization, elevated and not elevated prolactin) a Pearson’s chi-squared test will be used.

The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of FDOPA PET/CT will be determined for prolactinoma diagnosis. Receiver-operating characteristic (ROC) curves will be drawn to determine the cut-off value of SUVmax that would discriminate between functional and non-functional adenomas lesions.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2025
Actual
Date of last participant enrolment
Anticipated
1/02/2027
Actual
Date of last data collection
Anticipated
1/02/2028
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 28330 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 44543 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 319640 0
Charities/Societies/Foundations
Name [1] 319640 0
ANSTO/ANZSNM - Australia's Nuclear Science and Technology Organisation/Australian and New Zealand Society of Nuclear Medicine
Country [1] 319640 0
Australia
Funding source category [2] 319693 0
Charities/Societies/Foundations
Name [2] 319693 0
Neurosurgical Research Foundation
Country [2] 319693 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital (RAH)
Address
Country
Australia
Secondary sponsor category [1] 322144 0
None
Name [1] 322144 0
Address [1] 322144 0
Country [1] 322144 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318206 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 318206 0
Ethics committee country [1] 318206 0
Australia
Date submitted for ethics approval [1] 318206 0
10/04/2025
Approval date [1] 318206 0
16/07/2025
Ethics approval number [1] 318206 0
2025/HRE0015

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 143434 0
Dr James McNeil
Address 143434 0
Nuclear Medicine Department, Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 143434 0
Australia
Phone 143434 0
+61 08 7074 4574
Fax 143434 0
Email 143434 0
[email protected]
Contact person for public queries
Name 143435 0
James McNeil
Address 143435 0
Nuclear Medicine Department, Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 143435 0
Australia
Phone 143435 0
+61 08 7074 5400
Fax 143435 0
Email 143435 0
[email protected]
Contact person for scientific queries
Name 143436 0
James McNeil
Address 143436 0
Nuclear Medicine Department, Royal Adelaide Hospital, Port Road, Adelaide, South Australia, 5000
Country 143436 0
Australia
Phone 143436 0
+61 08 7074 5400
Fax 143436 0
Email 143436 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Ethical approval    2025HRE00115 McNeil- APPROVAL Letter.pdf


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.