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It’s normally the case that the higher the grade/Ki67 in Neuroendocrine Neoplasms (NENs), the less likely the tumours will have somatostatin receptors and therefore be able to take advantage of somatostatin receptor PET (SSTR PET) as the gold standard in nuclear imaging. This is why most grade 3 NENs will receive [18F]FDG PET/CT which finds glycolytic activity in the tumour and predicts an aggressive disease course and normally a higher histological grade. It can also add to prognostic outcomes, which in turn can add to therapy choice decisions.
There is an overlap though, particularly with the recognition of well-differentiated Grade 3 Neuroendocrine Tumours (NETs). It is known that some glycolytic activity might be present in some well-differentiated NETs, in particular, grade 3 and the upper range of 2 Neuroendocrine Tumours (NETs).
Conversely, increased uptake on [68Ga]DOTA-SSTR PET reflects receptor density and correlates with well-differentiated histology, more favourable outcomes and better response to PRRT.
The combination of imaging metabolism ([18F]FDG PET) and receptor (target) expression ([68Ga]DOTA-SSTR PET) – referred to as “dual PET imaging” – provides a comprehensive overview of the status of the disease throughout the entire body.
Reporting dual scan findings in a text-based report is complex particularly when physicians are already dealing with the complexity of NENs with the different primary locations. To address this, a group of physicians from UK and Australia previously proposed the NETPET score, a 5-point scoring system for dual PET reporting in subjects with metastatic NENs. The study was limited to Gastroenteropancreatic NENs (GEPNENs).
It summarises the information provided in [68Ga]DOTA-SSTR/[18F]FDG PET scans into a single parameter. This score correlated with overall survival in a small sample of 62 patients with NENs of various primaries. However, the single-centre nature of the study did not give a confident translation of the results into clinical practice.
Cue an international multicentre, and retrospective study (319 patients) aimed to investigate whether the NETPET score retained its prognostic power in a large group of patients with metastatic GEPNENs. The study conclusion said “Our large multicentre study validates the NETPET score as a robust prognostic biomarker of OS (overall survival) and TTP (time to progression) in patients with metastatic GEPNEN, and it represents a valuable complement to the prognostic algorithm. Dual PET imaging should be considered in all patients with a diagnosis of metastatic GEPNEN to guide the most optimal site for biopsy and inform the management approach.” The study also recommended the use of dual PET imaging for patients with rapidly progressing disease (irrespective of original biopsy findings), and those with grade 2 or well-differentiated grade 3 disease, in order to identify areas of potentially [18F]FDG avid, non-[68Ga]DOTATATE avid (i.e. discordant) disease. Such sites may not respond to SSTR-dependent therapies, thus influencing treatment selection. The study also acknowledged that economic considerations such as funding for dual tracers may limit the widespread adoption of routine dual PET imaging into clinical practice.
Chan, D.L., Hayes, A.R., Karfis, I. et al. Dual [68Ga]DOTATATE and [18F]FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms: a multicentre validation of the NETPET score. Br J Cancer (2022). https://doi.org/10.1038/s41416-022-02061-5
This is a developing area, and I can see it often inside my private patient group. I would say to those patients who are reading, this is not a standard approach across the board, and you should not expect to get dual PETs. The approximate boundary is contained in the studies above and the term ‘metastatic’ is another boundary clue. But interest in this approach is growing including this Canadian study I wrote about in 2021.
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