Ga68 Imaging Roland HUSTINX Division of Nuclear Medicine and Oncologic Imaging Centre Hospitalier Universitaire de Liège Belgium
68 Ga Produced by a 68 Ge/ 68 Ga generator Decays by positron emission in 89% yield Emax of the positron 1.9 MeV 18 F: 0.63 MeV T1/2 68 minutes
68 Ge/ 68 Ga Generators 68 68 Ge T1/2 271 days Decays into a 100% electron capture mode at 106 kev in 68 Ga. [ nat Ga(p,xn) 68 Ge] or [ 69 Ga(p,n) 68 Ge] reactions in the nominal energy range 25 30 MeV (ideally 28 MeV) A 24-30 MeV cyclotron at 250μA can produce about 500 mci 68 Ge after 4-5 days irradiation eight 50 mci-generators per batch (500+ generators a year). Issues: Availability of 68 Ge / cost Sterility 68 Ge breakthrough 68 Ga can also be produced with an 18 MeV cyclotron
68Ge/68Ga Generators: «chemicals Vs pharmaceuticals» 4 manufacturers Berlin, Germany Cape Town, South Africa Munich, Germany Fleurus, Belgium
Radiopharmacy
Somatostatin Receptors Imaging Johnbeck et al. Future Oncol. (2014) 10(14), 2259 2277
Comparison with Octreoscan Higher sensitivity More convenient for the patient Faster results Lower radiation burden Less expensive Buchmann et al. Eur J Nucl Med Mol Imaging (2007) 34:1617 1626 Krausz et al. Mol Imaging Biol (2011) 13:583-593
Carcinoid 111 In-Octreoscan 68 Ga-DOTANOC
Biodistribution & Dosimetry Sandstrom et al. J Nucl Med 2013; 54:1755 1759 Velikyan et al J Nucl Med. 2014;55:204-210.
Clinical performances: TATE vs TOC
Wild et al. J Nucl Med. 2013;54:364-372.
Pancreatic NET, grade 1, Ki67 <1% 68 Ga-DOTANOC FDG
Gastrinoma, surgery, increased chromogranin: relapse? FDG 68 Ga-DOTANOC
Medullary Thyroid Carcinoma 68 Ga-DOTANOC
Relapse of MTC: TP for LN & bone met, FN for liver mets
Pitfall: insulinoma
DOTATATE & DOTANOC, 1 year apart NET, treated by SS analogue 68 Ga-DOTATATE 68 Ga-DOTANOC
68 Ga-DOTANOC 68 Ga-DOTATATE
Midgut NET, liver & LN mets, treated by SS analogue DOTATATE & DOTANOC 8 months apart 68 Ga-DOTANOC 68 Ga-DOTATATE
Pitfall: radiation therapy 4 years before
«68 Ga-DOTATOC PET/CT was considerably cheaper than 111 In-DTPA-octreotide with respect to both material and personnel costs. Furthermore, by using 68 Ga-DOTATOC PET/CT considerably fewer additional examinations were needed reducing the consequential costs significantly.»
68GA-DOTA-XXX: Quantitative imaging and dosimetry for individualized treatment Velikyan et al. J Nucl Med 2014; 55:204 210
79%
Graf et al. Int J Radiation Oncol Biol Phys, Vol. 85, No. 1, pp. 68-73, 2013
Glu-CO-Lys(Ahx)-[68Ga(HBED-CC)] 68 Ga-PSMA-HBED-CC 68 Ga-PSMA-11 «68 Ga-PSMA» PSMA: type II transmembrane glycoprotein Low expression by prostate cells Hyperxpression by prostate adenocarcinoma Exact function not known
Sensitivity Vs PSA level Perera et al. EUROPEAN UROLOGY 70 (2016) 926 937
Biochemical relapse: comparison with Choline Lesions Patients Schwenk et al Eur J Nucl Med Mol Imaging (2017) 44:92 101
Diagnostic accuracy Perera et al. EUROPEAN UROLOGY 70 (2016) 926 937
PSA 0.88 ng/ml Doubling time 12 Mo (bladder ca)
PSA 0.7 ng/ml
PSA 1.61 ng/ml: local recurrence + bone met
Specificity? «However, since 68Ga-PSMA-11-PET/CT was introduced, the results prove the excellent specificity of this compound indicating that any uptake of 68Ga-PSMA-11 above local background in CT- or MR morphological visible lesions of PCa-patients should be regarded as highly suspicious for PCa» (Afshar-Oromieh et al, J Nucl Med. 2017 Jan 6.) False positive results: Other cancers: lymphomas, follicular thyroid ca, sarcoma, rectal ca, HCC, NET, RCC, etc. Benign tumors: thyroid adenoma, schwannoma, meningioma, etc. Benign lesions: fractures, Paget s, stroke, sarcoidosis, anthracosis, etc. Normal variants: cervicothoracic (stellate) & coeliac LN
Lung adenocarcinoma Pancreatic adenocarcinoma: PSMA & FDG
Theranostics
PET/CT V/Q scanning? Galligas: 50 MBq 68 Ga in a Technegas generator - 10 MBq are inhaled 68 Ga-MAA : 50 MBq I.V. Activity ratios V/Q: 1/4 ldct followed by 2 PET acquisitions of 6-9 min. each
99m Tc ventilation SPECT 99m Tc-MAA perfusion SPECT 68 Ga ventilation PET 68 Ga-MAA perfusion PET Hofman et al. J Nucl Med. 2011;52:1513-1519.
68 Ga-EDTA PET/CT Imaging and Plasma Clearance for Glomerular Filtration Rate Quantification Hofman M et al. J Nucl Med 2015; 56:405 409
68 Ga, ready to take off?
Conclusions 68 Ga: Highly attractive combination Physical and chemical properties Cost/availability Already a clinical difference maker (SSRI & prostate cancer) Regulatory issues to be solved Small batches (few patients)