PET/CT in Neuroendocrine Tumors: Evaluation of Receptor Status and Metabolism

doi:10.1016/j.cpet.2008.04.007

PET Clinics

Volume 2, Issue 3, July 2007, Pages 351-375

https://doi.org/10.1016/j.cpet.2008.04.007 Get rights and content

In-111 Octreoscan is considered the gold standard for imaging of neuroendocrine tumors (NET). However, in the absence of morphologic imaging correlation, the exact localisation of the tumor is often difficult. Also the sensitivity of PET imaging is more than Gamma camera (SPECT) imaging. Ga-68 labelled somatostatin analogs (SMS-R) are interesting radiopharmaceuticals for PET receptor imaging of NET. Some other radiopharmaceuticals e.g. F-18 DOPA can also be used to assess metabolism and functional status of NET. The importance of these radiopharmaceuticals, especially SMS-R increases in the absence of any specific biochemical marker or clinical parameter for follow-up of patients after therapy (eg peptide receptor radionuclide therapy, surgery, chemoembolisation, etc). New criteria based on molecular, metabolic and morphologic imaging needs to be developed for correct assessment of response to therapy for these slow-growing, solid tumors.

Section snippets

Biochemical Investigations

The most validated markers for the diagnosis and the follow-up of carcinoid tumors include²

1.
Chromogranin A (CGA)
2.
5-Hydroxyindoleacetic acid (urinary metabolite of serotonin)
3.
Gastrin
4.
Serotonin
5.
Pancreastatin
6.
Neurokinin A (substance K)

For follow-up, serial measurements of these markers are made every 3 to 6 months. The absolute value of CGA is not a determinate of tumor burden; nor can it rule out or confirm metastases. Changes in CGA level by 25% over the baseline are considered significant. There has

Positron emission tomography radiopharmaceuticals

PET radiopharmaceuticals can be directed toward assessing receptor expression or characterizing the intratumoral metabolic processes. The metabolic events and receptor targets that are currently being examined by PET are as follows (Table 1):

Receptor targets:
1.
Somatostatin receptor expression
2.
Miscellaneous other peptide receptors
Metabolic processes:
1.
Serotonin production pathway
2.
Biogenic amine storage
3.
Catecholamine transport
4.
Glucose metabolism

Receptor positron emission tomography or positron emission tomography/CT

The variable nature, indolent course, and possibility of multiple and unpredictable primary anatomic sites make it difficult to evaluate patients with NETs. Until recently, ¹¹¹In-octreotide-SPECT has been considered to be the gold standard for NET diagnosis. Hofmann and colleagues⁴⁰ have shown that ⁶⁸Ga-DOTA-TOC is superior to ¹¹¹In-octreotide SPECT in detecting upper abdominal metastases when CT was taken as the reference for comparison. In a recent study by Buchmann and colleagues,⁴¹⁶⁸

Role of metabolic positron emission tomography/CT

The role of metabolic PET/CT imaging techniques in the assessment of response to therapy is almost nonexistent, primarily because NETs are slow-growing tumors and no definitive therapy exists that influences cellular metabolism directly enough to be assessed by FDG or ¹⁸F-DOPA-PET/CT. In a preliminary study at the Zentralklinik Bad Berka, ⁶⁸Ga-DOTA-NOC-PET/CT was found to be superior to FDG-PET/CT for the early and accurate prediction of response to PRRT.⁸⁴ More data are needed to substantiate

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PET/CT in Neuroendocrine Tumors: Evaluation of Receptor Status and Metabolism

Section snippets

Biochemical Investigations

Positron emission tomography radiopharmaceuticals

Receptor positron emission tomography or positron emission tomography/CT

Role of metabolic positron emission tomography/CT

Semin Nucl Med

Peptides

Biochem Biophys Res Commun

Biochem Pharmacol

Lancet Oncol

Mol Imaging Biol

Semin Nucl Med

Med Hypotheses

Ann Oncol

Karzinoidtumore des Dünndarms

Frankf Z Pathol

Neuroendocrine tumors: a comprehensive guide to diagnosis and management

Endocrine tumors of the gastrointestinal tract and pancreas

Pathologisch-diagnostische Aspekte neuroendokriner Tumoren des Gastrointestinaltrakts

Der Onkologe

Histological typing of tumors: international histological classification of tumors in collaboration with 9 pathologists from 4 countries

TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system

Virchows Arch

Peptide receptors as molecular targets for cancer diagnosis and therapy

Endocr Rev

Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use

Eur J Nucl Med

Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands

Eur J Nucl Med

68Ga-DOTANOC: a first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5

Eur J Nucl Med Mol Imaging

DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals

Eur J Nucl Med Mol Imaging

Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors

Proc Natl Acad Sci USA

SST3-selective potent peptidic somatostatin receptor antagonists

Proc Natl Acad Sci USA

Processing of generator-produced 68Ga for medical application

J Nucl Med

68Ga-labelled DOTA-derivatised peptide ligands

Eur J Nucl Med Mol Imaging

Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting

Eur J Nucl Med Mol Imaging

99mTc-labeled vasoactive intestinal peptide analog for rapid localization of tumors in humans

J Nucl Med

Vasoactive intestinal peptide receptor scintigraphy

J Nucl Med

Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors

N Engl J Med

Improved kinetic stability of DTPA- dGlu as compared with conventional monofunctional DTPA in chelating indium and yttrium: preclinical and initial clinical evaluation of radiometal labelled minigastrin derivatives

Eur J Nucl Med Mol Imaging

Cholecystokinin-B/gastrin receptor binding peptides: preclinical development and evaluation of their diagnostic and therapeutic potential

Clin Cancer Res

Targeting of cholecystokinin-B/gastrin receptors in vivo: preclinical and initial clinical evaluation of the diagnostic and therapeutic potential of radiolabelled gastrin

Eur J Nucl Med

Pre-clinical evaluation of [(111)In-DTPA-Pro(1), Tyr(4)]bombesin, a new radioligand for bombesin-receptor scintigraphy

Int J Cancer

Cholecystokinin receptor imaging using an octapeptide DTPA-CCK analogue in patients with medullary thyroid carcinoma

Eur J Nucl Med

Unsulfated DTPA- and DOTA-CCK analogs as specific high-affinity ligands for CCK-B receptor-expressing human and rat tissues in vitro and in vivo

Eur J Nucl Med

Use of PET in neuroendocrine tumors: in vivo applications and in vitro studies

Q J Nucl Med

Positron emission tomography with 5-hydroxytryprophan in neuroendocrine tumors

J Clin Oncol

The metabolic anatomy of Parkinson's disease: complementary [18F]fluorodeoxyglucose and [18F]fluorodopa positron emission tomographic studies

Mov Disord

The added value of [(18)F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children

Eur J Nucl Med Mol Imaging

Evaluation of plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and plasma 3,4-dihydroxyphenylalanine (DOPA) as tumor markers in children with neuroblastoma

Scand J Clin Lab Invest

Whole-body 18F DOPA PET for detection of gastrointestinal carcinoid tumors

Radiology

Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters

Br J Cancer