MIBG scintigraphy

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Whole body scintigraphy 24 hours after intravenous administration of 123 iodine MIBG. Physiological occupancy of the thyroid, liver and urinary bladder. Pathological accumulation in a tumor of the left adrenal gland ( pheochromocytoma ).
Left: from the front. Right: from behind.

The MIBG scintigraphy (Metaiodbenzylguanidin scintigraphy, and adrenal medulla scintigraphy ) is a nuclear medicine examination method ( scintigraphy ) of the sympathetic nervous system . These include the adrenal medulla and the truncal cord . The most important indications of the investigation are the location of a pheochromocytoma , staging and therapy evaluation of a neuroblastoma , but also the differential diagnosis of Parkinson's disease and multiple system atrophy. MIBG, labeled with 131 iodine, can also be used for therapy.

application

Indications

The most important indications for the examination are in the field of oncology . It is used to identify and localize as well as to determine the stage (staging) and follow-up of the following tumors: pheochromocytomas , neuroblastomas , ganglioneuroblastomas , ganglioneuromas , paragangliomas , carcinoids , medullary thyroid carcinomas and Merkel cell tumors.

The specificity of the examination for tumors of the sympathetic nervous system is given as 100%, while the sensitivity for the detection of individual foci of a neuroblastoma is 80% and for the accuracy of the staging is 90 to 95%. There are MIBG-negative neuroblastomas and very small foci can evade detection.

Since 131 Iodine-MIBG is also used to treat these tumors, the examination can be used for the preparatory determination of the necessary dose (dosimetry) or to determine the success of the therapy in the course of the disease.

Indications outside of oncology are function tests of the adrenal medulla for hyperplasia and examinations of the sympathetic innervation of the heart muscle , salivary glands and lungs . Since the sympathetic innervation of the heart is regularly reduced in idiopathic Parkinson's disease , whereas it is normal in multiple system atrophies , MIBG scintigraphy can be used to differentiate between these two clinical pictures.

Contraindications

A pregnancy is considered, with few exceptions as an absolute contraindication for nuclear medicine examinations, breast-feeding as a relative contraindication. After an MIBG scintigraphy with 123 iodine, the breastfeeding woman should express and discard the milk for 48 hours. After an examination with 131 iodine, breastfeeding should be stopped .

Investigation principle and implementation

Structural formula of the MIBG

Metaiodbenzylguanidine (MIBG, Iobenguan) is a compound from the benzyl group of bretylium and the guanidine group of guanethidine . It was developed in the early 1980s to make tumors of the adrenal medulla visible. It is structurally similar to norepinephrine and is taken up by an active mechanism in neuroendocrine cells and stored in neurosecretory granules .

MIBG can be labeled with 131 I as well as 123 I (see list of iodine isotopes ) and for experiments with small animals also with 125 I. 123 iodine causes higher costs because it is produced in the cyclotron , but has more favorable physical properties ( shorter half-life , missing beta components of the radiation , less hard gamma radiation ). A higher usable activity results in a better image quality with a lower radiation exposure of the patient.

The thyroid gland should be blocked with perchlorate a few hours before the tracer is administered . The duration of the blockage depends on the isotope used .

The uptake of MIBG in the adrenal medulla is influenced by a number of drugs and groups of active substances, which - depending on the substance or substance class - should be discontinued about one to four weeks before the examination. These include: opioids , cocaine , tramadol , tricyclic antidepressants , sympathomimetics , labetalol , metoprolol , amiodarone , reserpine , bretylium , guanethidine , calcium antagonists , ACE inhibitors , phenothiazines , thioxanthenes .

123 I-MIBG-SPECT of the upper abdomen: significant accumulation in the left adrenal gland

When using 123 I-MIBG, planar full or partial body images are taken about 4 and 24 hours after the intravenous administration of the tracer , and SPECT images of the region of interest - usually the upper abdomen - after 24 hours . With 131 I-MIBG, recordings are usually made after about 24 and 48 hours. For SPECT recordings, very long recording times are often necessary with unsatisfactory image quality.

The uptake of the MIBG in various organs depends on their catecholamine excretion and adrenergic innervation . After intravenous administration, approximately 50% of the activity used appears in the urine within 24 hours . MIBG is usually mainly absorbed by the liver. A lower uptake takes place in the spleen , lungs , salivary glands , thyroid , skeletal and heart muscles . Normal adrenal glands are usually not visible, but in up to 15% of cases they can at least slightly accumulate. MIBG is absorbed to varying degrees in the nasal mucosa , lungs, gall bladder , colon , uterus and, depending on temperature, in brown adipose tissue. Free iodine can appear in the gastrointestinal tract and thyroid gland. Physiologically, bones do not enrich, so that increased activity in the bone must be viewed as involvement of bone marrow or bone marrow ( metastases ).

False negative results can occur in very small herds, in herds close to the primary tumor, in large metastases or in regions with high physiological storage. Further reasons can lie in the tumor itself ( heterogeneity , necrosis , lack of neurosecretory granules , lack of tracer absorption by the tumor) or be caused by pharmacological blockages.

Since the sympathetic innervation of the heart is reduced in Parkinson's disease , while it is preserved in multi-system atrophies , the MIBG scintigraphy of the chest can be used for the differential diagnosis of these two neurological symptoms at an early stage of the disease . A reduced accumulation of MIBG in the heart muscle with retained accumulation in the rest of the mediastinum (reduced heart / mediastinum ratio) speaks for idiopathic Parkinson's disease, and a normal heart / mediastinum ratio for atypical Parkinson's syndrome .

Risks and side effects, radiation exposure

Because of the low activity per weight (specific activity) compared to most other nuclear medicine examinations, a relatively large amount of tracer is required, pharmacological effects of the MIBG can occur. After the injection , palpitations , nausea , paleness and abdominal pain are occasionally observed. If the tracer is administered very slowly - over at least 5 minutes - these side effects are very rare.

The radiation exposure when using 400  MBq 123 I-MIBG is about 5  mSv . The liver is a critical organ with an organ dose of around 27 mSv. When using 80 MBq 131 I-MIBG, the equivalent dose (whole body) is around 11 mSv, the organ dose to the liver around 66 mSv. The required amount of activity is reduced in children depending on their body weight.

Alternatives

Pheochromocytoma

The diagnosis of pheochromocytoma is usually achieved by determining the catecholamines and their breakdown products in the blood plasma and urine . Sonography , computed tomography and magnetic resonance tomography can be used to determine the location . The strength of MIBG scintigraphy lies in the exclusion of further localizations.

In the case of metastatic pheochromocytoma, dedifferentiated metastases that cannot be detected by MIBG scintigraphy can be detected using 18 F - FDG - positron emission tomography (PET). Other suitable PET radiopharmaceuticals are 11 C - noradrenaline or - hydroxyephedrine . The better spatial resolution of PET is offset by logistical difficulties, since 11 C has to be produced in a cyclotron at the examination site with a half-life of only about 20 minutes, while 18 F-pharmaceuticals with a half-life of just under two hours can be transported to the examination site.

Neuroblastoma

In the early stages, the diagnosis is usually made by chance using ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI), which were made for other reasons. The bone scan can be used to distinguish between bone marrow and bone metastases are used.

Other neuroendocrine tumors

Many neuroendocrine tumors can also be visualized using somatostatin receptor scintigraphy . A DOTA-based PET / CT ( DOTATATE , edotreotide ) is more sensitive, and therefore currently the nuclear medical imaging of choice for G1 / G2 and possibly G3 NETs (not G3 NEC ). FDG-PET can be false negative , especially in tumors with a low G1 / G2 proliferation rate with a Ki67 <20% , but can be helpful for staging in low-differentiated neuroendocrine carcinoma (NEC) G3 with a high proliferation rate.

Parkinson's Disease

The diagnosis of Parkinson's disease is usually based on the clinical picture or by administering Parkinson drugs on a test basis . Other nuclear medicine methods are dopamine receptor scintigraphy and dopamine transporter scintigraphy . The advantage of MIBG scintigraphy lies in the ease with which it can be carried out and the distinction between Parkinson's disease and multiple system atrophies .

literature

Individual evidence

  1. ↑ a b c d M. Schmidt u. a. DGN recommendation for action (S1 guideline) mIBG scintigraphy in children. Updated version (2013) of the German translation (2002) of the EANM guideline (2002). (PDF; 392 kB) Retrieved September 21, 2019 .
  2. ^ A b S. Braune, M. Reinhardt, R. Schnitzer, A. Riedel, CH Lücking: Cardiac uptake of [123I] MIBG separate Parkinson's disease from multiple system atrophy. In: Neurology. Volume 53, Number 5, September 1999, pp. 1020-1025, PMID 10496261 .
  3. ↑ a b A. Lipp, P. Sandroni, JE Ahlskog u. a .: Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure . In: Arch. Neurol. . 66, No. 6, June 2009, pp. 742-750. doi : 10.1001 / archneurol.2009.71 . PMID 19506134 . PMC 2838493 (free full text).