Small Animal PET-Imaging with Scandium-44-DOTATOC Matthias Miederer 1 , Natalia S. Loktionova 2 , Franziska Graf 1 Nicole Bausbacher 1 , Hans-Georg Buchholz 1 , Markus Piel 2 , Mathias Schreckenberger 1 , Frank Rösch 2 Department of nuclear medicine 1 and Institute of radiochemistry 2 University Mainz, Germany
From kinetic-curve dosimetry to single time point surrogate parameters in humans
Correlation of dosimetry with single time point renal uptake ( 111 In-Octreotide measurements, calculation for 177 Lu therapy) 6 2.5 5 2 % of total injected activity % of total injected activity 4 1.5 3 1 2 0.5 1 0 0 0 0.5 1 1.5 2 2.5 3 3.5 0 0.5 1 1.5 2 2.5 3 3.5 number of disintegrations number of disintegrations Correlation with early uptake (4 h) Correlation mit late uptake (72 h)
Scandium-44: Background - Ideal for slow biological processes Scandium-44 - Applicable for Dosimetry Half live: 3.97 h - Three photon imaging without positron branching: 94.27 % reconstruction processes might be Photon emission (1157 keV): 99.9% possible 44 Ti/ 44 Sc radionuclide generator Half live 44 Ti: 60 years Activity: 185 MBq (5 mCi) elution efficacy for 44 Sc: >97 % breakthrough <5×10-5 % of 44 Ti
Methods 1. Labeling: in 0.25 M Ammonium Acetate buffer (pH=4) with 30 µg of DOTATOC specific activity: 1-3 MBq/µg 2. Nude mice with subcutanous xenograph (AR42J cells) 15-20 days Comparison: Distribution with and without excess cold DOTATOC Injected Activity: 3-7 MBq PET imaging: Focus 120, dynamic and static imaging PET-Reconstruction: OSEM, without attenuation correction Cross calibration with phantom measurements Organ activity determination: manual VOI (PMOD 2.95) 3. Sprague Dawley rats (n=6) for renal uptake study: Comparison 68 Ga/ 44 Sc
Scandium-44: image reconstruction F-18 AC Sc-44 NAC Sc-44 NAC Sc-44 BG-SUB W T air Sc-44 AC/BG-SUB 0.9 Sc-44 AC/BG-SUB 1.3 Sc-44 AC/BG-SUB 0.5 Sc-44 AC/BG-SUB 1.7
Calibration of the PET- Scanner (250 ml phantom) 60 PET measured activity concentration (kBq/ml) 50 y = 0.5409x 40 30 20 NAC center AC 0.9 center NAC peripheral 10 AC 0.9 peripheral Linear (NAC center) 0 0 10 20 30 40 50 60 70 80 Activity concentration (kBq/ml)
In vivo PET quantification at 60 min 60 50 40 %ID/ml Relative low binding, blockable by excess cold DOTATOC 30 20 10 0 tumor heart lung liver kidney muscle
Ex vivo quantification at 60 min 50 45 40 35 30 %ID/g 25 20 15 10 5 0 Heart Lung Liver Splen Stomach Kidney Tumor Muscle Blood Conventional biodistribution (n=1) confirms tumor binding and high renal accumulation
time activity curve in tumor tissue 200 180 160 activity concentration (kBq/ml) 140 120 100 80 Sc-44-DOTATOC 60 Ga-68-DOTATOC 40 20 Sc-44-DOTATOC (blocked) 0 0 10 20 30 40 50 60 70 80 90 100 time (min) Binding kinetic for 44 Sc-DOTATOC is similar to 68 Ga-DOTATOC
long term imaging with Scandium-44-DOTATOC Kidneys Tomor Heart 1 h 6 h 17 h 2 h Scandium-44-DOTATOC shows normal tumor binding but blood clearance is slow and renal retention is high
Comparision of PET Scans Kidneys Scandium-44- Tumor DOTATOC Heart 1 h Gallium-68- DOTATOC 1 h
Organ distribution of Ga-68-DOTATOC and Sc-44- DOTATOC 1 h after injection
Conclusion: •Scandium-44-DOTATOC (T 1/2 =4 h) shows typical SSR binding properties and allows acquisitions of time courses longer than 12 h. • Renal clearance is slow, possibly attributed to low specific activity and/or alterations due to Sc-44 chemistry
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