False-positive findings are because of contamination, most often urine contamination or any other contamination (salivary secretion). Using SPECT/CT can avoid misinterpretation of these findings.

The phaeochromocytoma is a catecholamine-secreting tumour of the chromaffin cells, and it is localized in the adrenal medulla to 85 % and occurs with an incidence of 1/100,000 people p.a.

Its characteristic symptoms are episodic headaches, palpitations, diaphoresis and paroxysmal or sustained hypertension [7]. The phaeochromocytoma occurs in isolation or as part of a syndrome, e.g. MEN2 syndrome, von Hippel-Lindau syndrome or neurofibromatosis type 1 (M. Recklinghausen). With widespread use of cross-sectional imaging, an increasing number of phaeochromocytomas are diagnosed incidentally, without the presence of symptoms or complaints by the patient. Incidental tumours, as well as tumours detected while screening patients with hereditary syndromes, tend to be smaller than symptomatic ones.

The first diagnostic method is plasma or urine measurements of catecholamines and their metabolites [7, 47]. If there is positive biochemical testing, further imaging is required, such as ultrasound, CT of the abdomen or MRI.

mIBG scintigraphy for detecting phaeochromocytomas or paragangliomas has been widely used for more than 25 years and has a reported high sensitivity and specificity of about 83–100 % and 85–100 %, respectively [48]. In the last 5 years, however, image quality and spatial resolution of other imaging methods, such as MRI with a high sensitivity for detection of tumours in the adrenal gland (which are usually hyperintense on T2-weighted images and hypointense on T1-weighted images), increased significantly [7, 49]; in addition, other functional imaging modalities such as ¹⁸F-DOPA PET/CT have been increasingly applied. Regarding this, some studies have been published that compared sensitivity and specificity of those other imaging methods to mIBG SPECT. They all share a significantly lower sensitivity for mIBG scintigraphy, from which it might be concluded that the mIBG scan has lost its monopoly position as the gold standard functional imaging method for phaeochromocytoma/paraganglioma. Critics find fault in its low spatial resolution, the long examination time of 24 h, the necessity of thyroid blockade, the interference with several medications and the significant tracer uptake in the normal adrenal medulla [50].

The disadvantage of the low spatial resolution may be largely compensated by the use of mIBG SPECT/CT; however, the other “disadvantages” remain. Additionally, limitations in terms of decreased sensitivity and specificity exist in several diseases, such as MEN2-related phaeochromocytoma, extra-adrenal, multiple or hereditary paragangliomas or metastatic disease, which may lead to a significant underestimation of the extent of disease in the mIBG scan with potentially inappropriate management. The particular strengths of mIBG SPECT/CT are detection of local recurrence, small extra-adrenal phaeochromocytomas, multifocal tumours or the presence of metastatic disease [27]. In patients with clinical or biochemical suspicion of phaeochromocytoma, SPECT/CT, compared to SPECT and planar imaging, has a significantly higher accuracy (Fig. 6.5) [51]. ¹²³I-mIBG scintigraphy, precisely with assistance of SPECT/CT, can serve for evaluation and dose calculation for ¹³¹I-mIBG therapy, from which patients may benefit [7, 52, 53].

Medullary thyroid carcinoma (MTC) is a quite rare thyroid tumour which occurs in 5–10 % of all thyroid carcinomas and arises from thyroid parafollicular C-cells, which are embedded in the thyroid but do not belong to the thyrocytes. It releases calcitonin, CEA and several other substances, such as chromogranin, serotonin, somatostatin and gastrin-releasing peptide.

A sensitive and specific marker for the occurrence of MTC is calcitonin, which is produced by the C-cells. An elevated calcitonin level (hypercalcitoninaemia) reflects a disorder, a reactive stimulation of the C-cells or impaired/disturbed degradation for calcitonin. There is a wide range of differential diagnoses for increased calcitonin levels, such as alcohol consumption, intake of various drugs (calcium, proton pump inhibitor, medication with calcitonin), hypercalcaemia and adrenal insufficiency. Also, a severe bacterial infection, a serious illness or a paraneoplastic syndrome can also cause a hypercalcitoninaemia. If reasons such as these are excluded, only C-cell hyperplasia (CCH, C-cell hyperplasia) and MTC remain as the two most frequent diagnoses. It should be noted that C-cell hyperplasia is associated specifically with males, in combination with autoimmune thyroiditis or hyperparathyroidism-associated hypergastrinaemia.

The reference values for basal calcitonin are higher in men than in women. Hypercalcitoninaemia should be confirmed in a second measurement. The interpretation of an elevated calcitonin level between10 and 100 pg/ml is ambiguous; only a basal calcitonin level >100 pg/ml is almost always accompanies an MTC. If available, for further diagnosis, a pentagastrin test should be carried out. If pentagastrin stimulation is not available, stimulation can also be performed with calcium, noting that after calcium stimulation, false-positive findings appear to be more common in female patients and patients with thyroiditis and thyroid neoplasia, other than MTC [54]. ^131/123I-mIBG uptake in MTC appears via the same molecular mechanisms, just as in other neuroendocrine tumours such as phaeochromocytoma [7].

Cross-sectional imaging studies employing neck, chest and three-phase abdominal CT scans or contrast-enhanced MRIs are recommended to rule out distant metastases, especially when suspicious lymph nodes are identified or when calcitonin levels are >400 pg/ml [55, 56].

There are also several radiotracers to mention, such as ^99mTc-(V)-DMSA, ¹²³I-mIBG and ¹¹¹In-labelled somatostatin analogue and the PET pharmaceuticals ¹⁸F-FDG, ⁶⁸Ga-DOTATOC and ¹⁸F-DOPA [57].

The use of ¹²³I-mIBG in MTC is not the gold standard procedure because of its low sensitivity, which is said to be approximately 35 % especially for familial/MEN-associated MTC. For sporadic MTC, data are superior. The specificity of mIBG is quite high and is approximately 95 % [57–61].

In summary, the role of ^131/123I-mIBG in the diagnostic evaluation of MTC is limited, but it still serves as an evaluation method for tentative therapy with ¹³¹I-mIBG [7].

Moreover, a combined diagnosis of ^131/123I-mIBG scan and somatostatin receptor scintigraphy (SRS) increases the sensitivity up to 100 % and seems to be the best practice to choose the most effective radiopharmaceutical with regard to therapy options [57].

The use of ^131/123I-mIBG SPECT/CT can serve as a follow-up to individual metastases and their responses to therapy, as SPECT/CT, more than planar imaging, simplifies localization and evaluation of the tumour burden.