Ga-68-DOTATOC -PET in the Management of Pituitary Tumours
Ga-68-DOTATOC -PET in the Management of Pituitary Tumours
Title: Gallium (GA) -68-DOTATOC -PET (positron emission tomography) in the management of
 pituitary tumours Medical product: Ga-68-DOTATOC in PET/computer tomography (CT) Route of
 administration: Intravenously Diseases of interest: Pituitary tumours Aim: To study the
 detection of pituitary tumours with Ga-68-DOTATOC -PET (Ga-PET) and to correlate the tracer
 expression to somatostatin receptor (sst) occurrence Study design: Prospective non-randomised
 case-control study with open design with GA-PET before and after pituitary surgery in
 patients with pituitary tumours Study population: patients with acromegaly (n=10), Cushing's'
 disease of pituitary origin (n=10), TSH (thyreotropin) producing tumours (TSHomas) (n=5) and
 non-functioning pituitary adenomas (NFPA) (n=20) Number of patients: 45 Inclusion criteria:
 Adult man or woman (over 18 years) and naïve, unoperated pituitary tumour with growth hormone
 (GH) or adrenocorticotrophic hormone (ACTH)) or TSH production or NFPA without treatment with
 somatostatin analogues (SSA) or dopamine agonists.

 Exclusion criteria: Patient who may not attend to the protocol according to the investigators
 opinion. Pregnancy or lactating. Isolated prolactin producing tumours. Overproduction of
 gonadotropins. Carcinoids ie ectopic corticotrophin realising factor (CRF) production. Known
 or suspected allergy to the trial product or related products.

 Controls: Adult patients with Thyroid associated ophthalmopathy (TAO) before iv steroid
 infusion (part of another study see this protocol)- Study variables: Tumour detection, Tracer
 uptake as Standardised uptake value (SUV) max (SUVmax), SUV hotspot and SUV mean in regions
 of interests (ROIs) Time schedule: Recruitment of patients 2015-2017. Study termination 3
 years later
Background The most common cause to pituitary insufficiency is the pituitary adenoma (PA). PA
 may be divided into hormone producing PAs and non-functioning PAs (NFPA). Normal pituitary
 tissue, as well as tissues from PAs, expresses somatostatin receptors (sst). Five subtypes of
 sst receptors has been characterized.

 Magnetic resonance tomography (MRI) presents anatomy, while in vivo diagnostics with
 somatostatin receptor scintigraphy (SRS) or position emission tomography (PET) reflect the
 functional properties of the tissue. The SRS have earlier been evaluated for diagnostics of
 pituitary diseases and has low discriminative ability to differ tumor tissue from normal
 pituitary tissue even though some secretory tumors and NFPA are seen. The superiority of the
 PET in diagnostics compared to the SRS is based on higher spatial resolution and a higher
 tumor to background ratio. Therefore it is of large interest to study Gallium 68 DOTATOC
 (Ga-PET) i small tumours that exhibit sst, such as in the pituitary, where high resolution is
 essential to discriminate from normal tissue and to evaluated residual tumor tissue
 postoperatively.

 Aim with the project

 To evaluate Ga-PET in the management of pituitary tumors and to seek the answer to the
 following questions:

 1. Is the method of value in primary diagnostics in PAs? Does Ga-PET contribute with more
 functional information than that given from an conventional MRI?

 2. Is the method of value in the follow-up, the detection of residual tumor tissue, and
 increase the possibility to differ scar tissue from true tumor?

 3. Can relapses of PA be detected earlier with Ga-PET than with conventional MRI?

 4. Are some of the sub-groups easier to detect that others??

 5. Can the pathological-anatomical findings and the immunochemical expression of sst be
 correlated to the PET findings?

 6. Can the treatment with somatostatin analogues be designed from the PET investigation and
 the sst analysis?

 Method The aim is to recruit 10 patients with acromegaly (GH-producing PA), 10 patients with
 Cushing's disease (ACTH-producing PA), 5 patients with TSH-producing PA (TSHoma) and 20
 patients with NFPA and to do Ga-PET before and after the pituitary surgery. In the Cushing
 patients, the TSHomas and in NFPA Ga-PET will also be dome after 3 years postoperatively to
 detect recurrences. At surgery, pituitary tissue is taken to investigate hormonal expression,
 sst and for further molecular genetic studies. At all PET occasions blood specimens from the
 patients are collected for future analyses. They will be kept in a freezer.

 If difficulties to separate the Ga-Pet up-take in tumors from normal pituitary tissue the
 tumor expression may be enhanced by a somatostatin injection before Ga-PET that suppresses
 normal tissue.

 The pituitary PET of pituitary tumours patients will be compared with the pituitary of
 patients with thyroid associated tumours performing PET according to the similar protocol in
 Another study

 Significance This study is a pilot study. Ga-PET has not been used in pituitary tumors but
 there is known from studies in patients with gastrointestinal neuroendocrine tumors that the
 pituitary is seen on GA-PET. This is a "proof of concept". It addresses some of the clinical
 problems in the management of pituitary tumors. If the questions addressed in this study will
 be answered in advantage for PET, PET may be a routine investigation and the patients may
 avoid invasive procedures and repeated MRI. In addition, the patients may have better
 information regarding cure or not. If not, the treatment may be tailored from the sst
 receptor expression. This is of great importance for the patients and for the health care
 system.
Inclusion Criteria:

 -  Naïve, unoperated pituitary tumour with GH or ACTH or TSH production or NFPA without
 treatment with somatostatin analogues or dopamine agonists.

 Exclusion Criteria:

 -  Patient who may not attend to the protocol according to the investigators opinion.

 -  Pregnancy or lactating

 -  Isolated prolactin producing tumours

 -  Overproduction of gonadotrophins

 -  Carcinoids ie ectopic CRF production

 -  Known or suspected allergy to the trial product or related products.