Theranostics: From molecular imaging using PET/CT to personalised therapy of over 1100 patients with neuroendocrine tumours (NETs)


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Harshad R Kulkarni1
1ENETS Center of Excellence, Zentralklinik Bad Berka, Germany

Abstract

68Gallium is a positron emitter (T1/2 68 min) which can be produced from a generator in a convenient, ‘in-house' preparation and used for labelling of peptides e.g. somatostatin analogues (SA) like DOTATOC/DOTANOC/DOTATATE for molecular imaging of SSTR expressing tumours. Since 2004, we have performed over 8500 68Ga-PET/CT studies in patients with neuroendocrine tumours (NETs) and have established SSTR PET/CT as the new gold standard for imaging G1 and G2 NET (staging, restaging, therapy response evaluation and detection of unknown primary NET).

The same peptides can be labelled with 177Lutetium or 90Yttrium for peptide receptor radiotherapy (PRRT), a form of personalised treatment (theranostics approach). A German multi-institutional registry study with prospective follow up in 450 patients indicates that PRRT is an effective therapy for patients with G1-2 neuroendocrine tumours with a survival advantage of several years compared to other therapies and only minor side effects. Median overall survival (OS) of all patients from the start of treatment was 59 months. Median progression-free survival (PFS) measured from last cycle of therapy accounted to 41 mo. Median PFS of pancreatic NET was 39 mo. Similar results were obtained for NET of unknown primary (median PFS: 38 months) whereas NET of small bowel had a median PFS of 51 months. Side effects like grade 3-4 nephro- or haematotoxicity were observed in only 0.2% and 2% of patients, respectively. Fractionated PRRT with lower doses of radioactivity given over a longer period of time (Bad Berka Concept) results in excellent therapeutic responses. By this approach, severe haematological and/or renal toxicity can be avoided and quality of life/clinical symptoms can be significantly improved.

The concept of theranostics has now been translated to other malignancies as well (e.g. prostate cancer) and current state and future perspectives of this fascinating approach will be discussed.