WP1 aims at the development, optimization and testing of an integrated imaging technology for intraoperative and endoscopic use for IGS as well as tPDT . The specific aims of WP1 are

1. To develop a clinical near-infrared fluorescence (NIRF) laparoscope, compatible with the beta-cell specific Exendin-800CW optical tracer developed in WP2. In addition, we aim to develop a fully integrated hybrid NIRF and photodynamic therapy compatible clinical laparoscope for theranostic purposes in combination with the Exendin-700DX tracer developed in WP2
2. To design and build an optical coherence microscopy (OCM) system for label free ex vivo pancreas and islet cell imaging for monitoring and optimizing the PDT therapy on established rodent models at a cellular level in conjunction with the hybrid laparoscope
3. To develop a portable OCM desk-top device to be used as validation of resection margins ex vivo for image-guided histopathology purposes.

WP lead: 02 SOP (Ton van den Hoven)
WP members: 01 SKU, 02 SOP, 03 UMCG, 05 Charité, 08 UCL, 11 UL2, 12 EPFL, 13 EXA

Based on existing experience, Exendin will be optimized as a tracer molecule for IGS , tPDT and PRRT in CHI and AHH using in vitro and in vivo models. For personalized treatment of patients, concepts need to be developed in animal models for quantitative therapy planning and treatment.
The specific aims are:

1. To optimize tracers for PRRT , IGS and tPDT of CHIand AHH
2. In vitro and in vivo evaluation of tracers in animal models and patients (in close collaboration with WP3)
3. Preparation of the clinical studies by collecting all necessary preclinical data (in cooperation with WP3)
4. Development of 3D dosimetric concepts based on beta cell specific microdosimetry in animals for planning and evaluation of PRRT and tPDT

WP lead: PSI (Martin Béhé)
WP members: 01 SKU, 02 SOP, 03 UMCG, 05 Charité, 06 UHBS, 09 UHE, 10 UTU, 11 UL2

In order to guarantee for the seamless translation of novel tracer molecules into the clinics, WP 3 focuses on the production and delivery of clinical tracers according to all European and national guidelines and legislation. BetaCure partners UMCG and SKU both dispose over fully equipped GMP facilities for production of clinical grade tracer molecules. Qualified persons from both institutions will authorize delivery of the compounds to other BetaCure partners and ensure rapid delivery as well as quality control. In close cooperation with WP2, translational testing will be performed for final validation of the products before clinical application, which will take place in close cooperation with WP4.

WP lead: 03 UMCG (Gooitzen van Dam)
WP members: 01 SKU, 03 UMCG, 04 PSI, 05 Charité, 06 UHBS, 07 UBERN, 10 UTU, 14 TRM, 17 piCHEM

In WP 4, the BetaCure consortium aims at evaluation and optimization of quantitative pre-operative imaging for treatment planning including individual planning of IGS . At the end of the runtime, BetaCure will define an optimal diagnostic approach for AHH and CHI and have identified an effective clinical approach for individualized planning of IGS and tPDT.
The specific aims are:

1. Clinical validation and comparison of the developed/improved pre-operative imaging methods in patients with{tip Adult Hyperinsulinemic Hypoglycemia} AHH{tip} / CHI in order to determine the optimal pre-operative imaging strategy for planning IGS.
2. Optimizing quantitative pre-operative imaging in patients with focal/diffuse CHI/AHH and correlation with surgical outcome as well as reduction of radiation exposure.
3. Clinical validation, optimization and comparison of the newly developed intra-operative imaging methods (IGS) in patients with AHH/CHI and correlation with surgical outcome.

WP lead: 06 UHBS (Damian Wild)
WP members: 01 SKU, 02 SOP, 03 UMCG, 05 Charité, 06 UHBS, 07 UBERN, 08 UCL, 09 UHE, 10 UTU, 11 UL2

WP 5 aims at evaluation and optimization of tPDT , finally delivering the proof-of-principle in adult patients and possibly also in CHI patients.
The specific aims of WP 5 are to:

1. Determine the in vitro and in vivo efficacy of tPDT by Exendin-4-700DX
2. Execute a full evaluation for clinical translation of cGMP synthesized Exendin-4-700DX (includes cGMP production, testing (animal toxicity testing) and IMPD writing)
3. Execute small smart feasibility study in adult patients with pancreatic cancer and AHH
4. To execute a feasibility study of tPDT in paediatric patients with CHI .

WP lead: 03 UMCG (Gooitzen van Dam)
WP members: 01 SKU, 02 SOP, 03 UMCG, 04 PSI, 05 Charité, 08 UCL, 11 UL2

WP 6 plays a central role in the interaction of BetaCure partners aiming at building up intersectoral expertise, training of experts within and outside of the consortium and definition and implementation of standards for personalized diagnostics and treatment in CHI and AHH patients. In addition, in order to obtain quantitativeSPECT and PET data of the highest quality, all scanners used for the clinical studies will be calibrated and certified
The specific aims of WP 6 are:

1. Training of scientists including training for clinical studies
2. Definition and implementation of standards for the clinical studies including scanner calibration and data management
3. Dissemination of BetaCure results towards the scientific community and the general population with a focus on contact with patient organizations
4. Training of physicians and scientists outside of the consortium.

WP lead: 15 EARL (Sabine Ettinger)
WP members: 01 SKU, 14 TRM, 15 EARL, 16 concentris

Effective project management is a central element of successful research. This is because large research projects entail a lot of administrative work. The following objectives will be actively pursued by WP7:

1. Make BetaCure achieve its objectives and to deliver in time, budget and quality its milestones and deliverables
2. Help the consortium abide by the regulations and contractual obligations according to the grant agreement, its annexes and the consortium agreement
3. Look after the project`s finances and to report them properly to the European Commission
4. Establish a communication infrastructure which enables the partners to communicate efficiently and to stay connected for the run-time of the project
5. Preserve the rights of the partners regarding intellectual property and to act as a mediator in case of disputes

WP lead: 01 SKU (Martin Gotthardt) – 16 concentris (Andrea Wohner)
WP members: 01 SKU, 16 concentris