Case betacure

The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007– 2013) under grant agreement n° 602812

BetaCure: Personalized diagnosis and treatment of hyperinsulinemic hypoglycaemia caused by beta-cell

pathologywww.betacure.eu

Pirjo NuutilaTurun PET-keskus

Turku yliopisto, TyksTurku

EU FP7 HEALTH.2013.1.2-1: Development of imaging technologies for therapeutic interventions in rare diseases

18F-DOPA PET as a Tool to Localize an Insulinomaor -Cell Hyperplasia in Adult Patients

Insulinoma in adults: Insidence 1-4 /1 milj., diameter < 2 cm ***In 2001, a 34-year-old female patient with severe symptoms and focal ß-cell hyperplasia imaged with 18F-DOPA PET. Focus in the head of the pancreas.Operation -> focal hyperplasia -> cured

The first aricle: 10 adult patients8 insulinomas2 hyperplasia)

Kauhanen, Nuutila, JCEM 2007

* Conventional imaging CT, MRI: not informative• Functional tests invasive,not sensitive(Arterial Ca stimulation / venous sampling

(ASVS), pancreatic venous sampling (PVS) through intrahepatic portalcatheterization

Congenital hyperinsulinism (CHI), 1/50 000 birth

• All islets are affected•Conservative Treatment -> near-total pancreatectomy• Long-term outcome: High risk of diabetes

Diffuse Focal

•Focal adenomatous hyperplasia• Paternally inherited recessive mutations in SUR1, Kir6.2• Treatment: Selective resection of the focal lesion*• Outcome: Cure

Pancreatic -cell mass/function FDOPA PET in 20 CHI patients at the Turku PET Centre since 2002

Focus

Otonkoski, Nuutila et al, Diabetes, 2006

Pancreatic focal cell hyperplasia in infants can be localized using 18F-DOPA in infants

Exendin SPECT/PET tracers• 111In-Exendin SPECT/CT scan of a

patient with a history of 17 years of recurrent hypogly-caemias in whom no focus could be identified (18F-DOPA/111In-octreotide/MRI/endoscopic & intraoperative ultrasound).

• Increased beta cell activity in the tip of the pancreatic tail and the pancreatic head (arrow)

• Microautoradiography showing specific uptake in the beta-cells/islets ( rat pancreas dissected 1 h p.i. of 15 MBq[Lys40(111In-DTPA)]exendin-3)

AIMS

• In Finland• Optimization and characterization of tracers (18F-Exendin, preclinical ) • Optimized pre-operative imaging will be performed using Ga-68- Exendin by PET for

identification of foci and for determination of the beta cell mass• adult hyperinsulinemic hypoglycaemia (AHH) : ethical approval, Fimea in progress• Congenital hypoglymia in infancy (CHI) : pending

WP 5, Photodynamic TherapyUMCG, van Dam, Nature Med 2011

Turku PET Centre• Finnish national research institute started in 1974, status in 1995• Owned by University of Turku (UTU), Åbo Akademi University, Turku

University Hospital• Expertise in PET tracer development, preclinical and clinical PET

research, diagnostic services, and contract research for the pharmaceutical industry.

• More than 130 staff members and investigators 3 cyclotrons, 16 hot cells for GMP level PET tracer production

• PETMRI, 2 PETCT, 2 PET, MRI, digital US, a small animal PET/CT• ~100 international publications annually

Betacure team in TurkuP rof Pirjo Nuutila, PI• Prof Pirjo Nuutila, PI

• Docent Marko Seppänen, MD: diagnostic services• Dr. Saila Kauhanen, MD,

• Prof. Olof Solin, PhD, coordination of radiochemistry • Chen Yen-Bin, PhD:Peptide chemistry, labeling syntheses• Pauliina Lehtiniemi, MSc• Kirsi Mikkola, MSc; preclinical studies

• .

The research leading to these results has received funding from the European Community’sSeventh Framework Programme (FP7/2007– 2013) under grant agreement n° 602812