68Ga-DOTA-NOC PET/CT for the imaging of disease activity in neurologic and cardiac sarcoidosis.

Sarcoidosis is a systemic granulomatous disease most frequently affecting the
lungs, although (severe) neurological and cardiac complications are also
reported. Currently, there is no gold standard for the assessment of
sarcoidosis and disease activity is determined by a combination of clinical
investigation, laboratory analysis, chest radiography, 18F-FDG PET/CT and lung
function tests. The detection of active neurological and cardiac lesions is
especially challenging and there is an unmet clinical need to distinguish
active inflammation from inactive disease. In-vivo imaging of (sarcoid)
granulomas can be performed using radiolabelled somatostatin analogues and
sites revealed in this way are considered to represent active disease. In the
past years maging quality was hampered by to the absence of PET tracers, but
recently Ga-68 labelled somatostatin analogues have come available.

We hypothesize that 68Ga-DOTA-NOC SSTR-PET/CT is a sensitive and highly
specific technique that could provide in a tool that distinguishes active
inflammation from inactive disease, and can aid in the clinical decision making
process. In this way immunosuppressive therapy can be initiated in those
patients who are expected to benefit clinically, with the potential of
monitoring treatment effects. Furthermore, patients without active
inflammation could be withheld immunosuppressive therapy, thereby eliminating
the risk of side effects in a group where no clinical benefit is to be
expected.

The primary objective of this study is to evaluate the role of 68Ga-DOTA-NOC
PET/CT in the imaging of disease activity in suspected neurological and cardiac
sarcoidosis and to assess the sensitivity and specificity of 68Ga-DOTA-NOC
PET/CT.

We hypothesize that 68Ga-DOTA-NOC SSTR-PET/CT is a sensitive as well as highly
specific method to measure cardiac and neurological sarcoidosis disease
activity. This hypothesis is based on known SSTR expression in sarcoid
granuloma, and the results of SRS in sarcoidosis. 68Ga-DOTA-SSTR-PET/CT is the
gold standard for diagnosis of NET and could prove superior to SRS in
sarcoidosis as well.

As secondary objective we plan to correlate the clinical response to
immunosuppressive therapy with quantitative uptake measures (myocardial SUVmax
and SUVmean for 68Ga-DOTA-NOC). Since SSTR-PET/CT reflects the inflammatory
activity within the sarcoid granuloma, we hypothesize that 68Ga-DOTA-NOC uptake
predicts the response to immunosuppressive therapy.

The study is a prospective single-center pilot (proof of principle) study of
consecutive patients with suspected cardiac or neurological sarcoidosis at the
Centre of Interstitial Lung diseases, Department of Pulmonology of the St
Antonius Hospital.

The study group will be divided into two groups with either suspected cardiac
(n = 30) or neurological (n = 10) sarcoidosis.

In addition to the St Antonius Hospital sarcoidosis work-up, the additional
medical research will entail a 68Ga-DOTA-NOC PET/CT. The administered dose will
be approximately 150 MBq 68Ga-DOTA-NOC. With a dose equivalent of 1.7 x 10-2
mSv/MBq this will entail an additional effective radiation dose of 2.55 mSv
[25]. The effective radiation dose of the CT acquisition of the chest for
attenuation correction and localisation will be 1 mSv resulting in a cumulative
effective dose of 3.55 mSv for the PET/CT procedure per subject. This is
comparable to 1.4 times the yearly radiation dose for the Dutch population.

The amount of DOTA-NOC, an octreotide analogue, used for 68Ga-DOTA-NOC PET/CT
involves a maximum of 40 microgram. This is in conformance with the limit of 50
microgram in the Ph. Eur. monograph as well as the EANM guideline on PET/CT
tumour imaging with 68Ga-DOTA-conjugated peptides, as this amount is expected
to have no clinically significant pharmacological effect. 68Ga-DOTA-NOC is a
radiopharmaceutical used worldwide since 2003 and is included in the previously
mentioned 2010 EANM guideline.

68Ga-DOTA-NOC PET/CT has been in routine use for the diagnosis of NET in the St
Antonius Hospital since September 2014, in accordance with the local
pharmacovigilance procedure for radiopharmaceuticals without a marketing
authorization.