Present and future of targeted molecular imaging and therapy (theranostics) as a personalized pathway to diagnosis and treatment

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 labeling of peptides, e.g. somatostatin analogues (SA) like DOTATOC or DOTATATE for molecular imaging of SSTR expressing tumors. Since 2004, we have performed over 8,000 ⁶⁸Ga PET/CT studies in patients with neuroendocrine tumors (NET) 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 labeled with ¹⁷⁷Lutetium or ⁹⁰Yttrium for radionuclide therapy, a form of personalized treatment (THERANOSTICS approach). PRRT is based on the receptor-mediated internalization of SA, a concept which was introduced at our center in 1999 and since then we have treated over 1,200 patients with a total of 4,000 therapy cycles using ¹⁷⁷Lu and ⁹⁰Y labeled peptides. Several clinical trials indicate that PRRT can deliver effective radiation doses to tumors. 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 tumors, irrespective of previous therapies, 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 mol whereas NET of small bowel had a median PFS of 51 months. Side effects like °3-4 nephro- or hematotoxicity were observed in only 0.2% and 2% of patients respectively. PRRT is highly effective in the management of NET, even in advanced cases. In patients with progressive neuroendocrine tumors, fractionated, personalized PRRT with lower doses of radioactivity given over a longer period of time (Bad Berka Concept using sequential (DUO) PRRT) results in excellent therapeutic responses, By this approach, severe hematological 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 using PSMA as ligand and ⁶⁸Ga/¹⁷⁷Lu as diagnostic/therapeutic pair) and current state and future perspectives of this fascinating approach - which enables personalized treatment of malignant neoplasms - will be discussed. (author)