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. Author manuscript; available in PMC: 2018 Mar 1.
Published in final edited form as: Clin Nucl Med. 2017 Mar;42(3):211–213. doi: 10.1097/RLU.0000000000001504

Relevant discordance between 68Ga-DOTATATE and 68Ga-DOTANOC in SDHB-related metastatic paraganglioma: is affinity to somatostatin receptor 2 the key?

Ingo Janssen 1,*, Katherine I Wolf 1,*, Chan H Chui 2, Corina M Millo 3, Karel Pacak 1
PMCID: PMC5290153  NIHMSID: NIHMS833231  PMID: 28033222

Abstract

Pheochromocytomas/paragangliomas (PPGLs) are somatostatin receptor 2 overexpressing tumors. 68Ga-DOTA-peptide imaging has recently shown excellent results in the detection of metastatic lesions in these tumors. However, currently used 68Ga-DOTA-peptides show different somatostatin receptor affinities. Here, we report the remarkable differences in a patient who was imaged with 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT within a 7-month period of time. The patient presented with a nearly negative 68Ga-DOTANOC PET/CT scan, while on 68Ga-DOTATATE PET/CT, multiple highly positive lesions were identified.

Keywords: pheochromocytoma, paraganglioma, metastatic, positron emission tomography, 68Ga-DOTATATE, 68Ga-DOTANOC

Since the majority of the lesions were stable on CT (0.6 cm in the right upper compared to 0.8 cm in December 2014 and June 2015, respectively) it is very suggestive that this remarkable discordance between 68Ga-DOTANOC and 68Ga-DOTATATE is not related to progressive disease, but to the different affinity profiles of the different DOTA-peptides to somatostatin receptors (SSR). 68Ga-DOTATATE has an approximate 9-times higher affinity to SSR22, mainly overexpressed in PGLs3, when compared to 68Ga-DOTANOC, which has been shown to have a high affinity for SSR34 – recently discovered to be expressed in succinate dehydrogenase-deficient PPGLs5. Immunohistochemical staining of the primary and lung metastases confirmed strong SSR2 expression in the lesions with negative staining of the surrounding normal tissue.

The phenomenon of additional lesions on 68Ga-DOTATATE scans compared to 68Ga-DOTANOC scans or vice versa for different neuroendocrine tumors or even additional findings in a post treatment scan after 177Lu-DOTATATE therapy compared to the pre-treatment 68Ga-DOTANOC scan have already been previously reported6–8. However, to our best knowledge, not to this extent. These intra-individual differences in the performance of different DOTA-peptides are of important significance, since they should guide appropriate 68Ga-DOTA-peptide functional imaging and follow-up, as well as the appropriate DOTA-peptide choice for receptor radionuclide therapy (PRRT).

FIGURE 1.

FIGURE 1

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A ten year-old girl with a succinate dehydrogenase subunit B (SDHB) mutation was diagnosed with a 3.5 × 5.2 × 5.0 cm upper abdominal mass in January 2014. The abdominal mass showed intense uptake on 68Ga-DOTATOC positron emission tomography (PET)/computed tomography (CT) (A, B). Several sub-centimeter lung nodules were seen on CT, with two lung nodules on the right side barely 68Ga-DOTATOC positive (C, D). Histopathology confirmed an abdominal PGL along with PGL-related lung metastases.

FIGURE 2.

FIGURE 2

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In December of 2014, the patient underwent a 68Ga-DOTANOC PET/CT scan for follow-up. The PET portion of the scan was initially read negative (A), despite the CT component showing many, apparently stable, pulmonary lesions highly suspicious for lung metastases. In our retrospectively performed review, some lung nodules appeared faintly 68Ga-DOTANOC positive (B, C).

FIGURE 3.

FIGURE 3

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Because of increasing normetanephrine levels suggestive for progressive disease, the patient was transferred to our institution in June 2015. After extensive discussion, and based on our experience with 68Ga-DOTATATE in SDHB positive patients1, the decision was made to perform a 68Ga-DOTATATE PET/CT scan. Surprisingly, this scan was very positive (A), detecting several lung- and also bone lesions, with standardized maximum uptake levels (SUVmax) up to 49.6 (B), which were not, or only faintly positive, on 68Ga-DOTANOC 6 months before (see Figure 2). The positive lesions on 68Ga-DOTATATE PET/CT were likewise confirmed by 18F-FDG PET/CT.

Acknowledgments

Funding: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health

Footnotes

Conflict of interest: The authors claim no conflicts of interest.

References

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