Theranostics for Neuroendocrine Cancer – A Find and Destroy Mission


Neuroendocrine Cancer – we’re coming to get you! Graphic courtesy of Advanced Accelerator Applications

Theranostics is a joining of the words therapeutics and diagnostics. You may also see it conveyed as ‘Theragnostics’ and these terms are interchangeable.  The basic aim of theranotistics is to find and then destroy the ‘bad guys‘.  With Neuroendocrine Cancer, finding the tumours (the bad guys) can often be a challenge – they can be small and/or difficult to find – they are sometimes expert at camouflage.  Moreover, once found, they can then be difficult to treat (destroy), as they can often prove resistant to conventional cancer drugs and many are inoperable due to sheer quantity, spread and positioning.  When they are found and identified, it’s also really helpful to know from the intelligence gathered, how successful the destroy (therapeutic) part of the mission might be.  That is the beauty of theranostic pairing, i.e. the use of the same agent in the diagnostics – the ability to find, estimate likely success criteria and then hopefully destroy – or at least reduce the capability of the tumours and extend life.

A great example of an approved Theranostic Pair in Neuroendocrine Cancer, is the combination of the Somatostatin Receptor based Ga68  PET scan using NETSPOT or SomaKit TOC™ (US/Europe respectively) and Peptide Receptor Radiotherapy (PRRT) using Lutathera which both target NETs expressing the same somatostatin receptor, with PRRT intended to kill tumor cells by emitting a different kind of low-energy, short-range radiation than that of the diagnostic version. As mentioned above, the Ga68 PET scan can give a reasonably indication of therapeutic success using PRRT based on measurements taken during the scan (too complex for this article).

Theranostics – a step towards personalised medicine – graphic courtesy of Advanced Accelerator Applications.

THERANOSTICS – FIND

Octreoscan vs Ga68 PET

Ga68 PET 

Newer imaging agents targeting somatostatin receptors (SSTR) labelled with 68 Ga have been developed, namely, DOTATATE, DOTATOC and DOTANOC. They are collectively referred to as SSTR PET.

The full titles of the 3 types are:

68Ga-DOTA-Phe1-Tyr3-Octreotide (TOC),
68Ga-DOTA-NaI3-Octreotide (NOC),
68Ga-DOTA-Tyr3-Octreotate (TATE).

The main difference among these three tracers (DOTA-TOC, DOTA-NOC, and DOTA-TATE) is their variable affinity to SSTR subtypes. All of them can bind to SSTR2 and SSTR5, while only DOTA-NOC shows good affinity for SSTR3.

These agents have several benefits over In111-pentetreotide (Octreotide scan), including improved detection sensitivity, improved patient convenience due to the 2 hour length of the study (compared to 2 or 3 days with Octreoscan), decreased radiation dose, decreased biliary excretion due to earlier imaging after radiotracer administration, and the ability to quantify uptake. The quantification of the uptake can help decide whether a patient is suitable for PRRT. Eventually, all Octreotide scans should be replaced with SSTR PET.  To confirm the advantages of SSTR PET over Octreotide scans, a study comprising 1,561 patients reported a change in tumour management occurred in over a third of patients after SSTR PET/CT even when performed after an Octreotide scan. Worth pointing out that SSTR PET is replacing the ageing Octreotide scan and not conventional imaging (CI).  You can see the recommended scenarios for use of SSTR PET in this article published by the Journal of Nuclear Medicine

Ga68 PET scans have been in many locations for some time. Current excitement is focused on USA locations with Ga68 PET (NETSPOT) only recently approved (DOTATATE). Other countries/scan centres may use one of the other types of imaging agent.

Read much more about this scan in my detailed article on Ga68 PET here.

So SSTR PETs above have the ability to find and estimate likely success criteria for therapy.  We are now in a position to move on to ‘THERApy’ – e.g.  Peptide Receptor Radiotherapy or PRRT.

THERANOSTICS – DESTROY

click on picture to watch video

Lutathera® (note the ‘THERA’ which makes up the brand name)

Definitions:

Europe Approval: LUTATHERA®(lutetium (177Lu) Oxodotreotide) is indicated for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEPNETs) in adults.

USA Approval: LUTATHERA® (lutetium Lu 177 dotatate) is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults.

For commercial purposes, the drug may be slightly different on a regional basis. For all intents and purposes it does the same job.

As an example of how the drug is administered, please watch this short video from the European site:

Video courtesy of Advanced Accelerator Applications

Please see the following post for a summary of PRRT activity worldwide.  Please note this linked article is not designed to contain a list of every single location or country available – please bear that in mind when you read it – CLICK HERE

I’m very grateful to the team at Advanced Accelerator Applications for allowing me to use their site for graphics and videos.

Thanks for reading

Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!

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