Small Animal PET-Imaging with Scandium-44-DOTATOC

Matthias Miederer1, Natalia S. Loktionova2, Franziska Graf1

Nicole Bausbacher1, Hans-Georg Buchholz1, Markus Piel2, Mathias Schreckenberger1, Frank Rösch2

Department of nuclear medicine1 andInstitute of radiochemistry2

University Mainz, Germany

From kinetic-curve dosimetry to single time point surrogate parameters in humans

Correlation of dosimetry with single time point renal uptake(111In-Octreotide measurements, calculation for 177Lu therapy)

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number of disintegrations

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Correlation with early uptake (4 h) Correlation mit late uptake (72 h)

Scandium-44: Background

44Ti/44Sc radionuclide generator

Half live 44Ti: 60 years Activity: 185 MBq (5 mCi) elution efficacy for 44Sc: >97 %breakthrough <5×10-5 % of 44Ti

Scandium-44Half live: 3.97 hpositron branching: 94.27 %Photon emission (1157 keV): 99.9%

- Ideal for slow biological processes- Applicable for Dosimetry- Three photon imaging withoutreconstruction processes might be

possible

Methods

1. Labeling: in 0.25 M Ammonium Acetate buffer (pH=4) with 30 µg of DOTATOCspecific activity: 1-3 MBq/µg

2. Nude mice with subcutanous xenograph (AR42J cells) 15-20 days

Comparison: Distribution with and without excess cold DOTATOCInjected Activity: 3-7 MBqPET imaging: Focus 120, dynamic and static imagingPET-Reconstruction: OSEM, without attenuation correction

Cross calibration with phantom measurementsOrgan activity determination: manual VOI (PMOD 2.95)

3. Sprague Dawley rats (n=6) for renal uptake study: Comparison 68Ga/44Sc

Scandium-44: image reconstruction

F-18 AC Sc-44 NAC

Sc-44 AC/BG-SUB 0.9 Sc-44 AC/BG-SUB 1.3

Sc-44 NAC Sc-44 BG-SUB

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Sc-44 AC/BG-SUB 0.5 Sc-44 AC/BG-SUB 1.7

y = 0.5409x

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Activity concentration (kBq/ml)

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NAC center

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Linear (NAC center)

Calibration of the PET- Scanner (250 ml phantom)

In vivo PET quantification at 60 min

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tumor heart lung liver kidney muscle

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Relative low binding,blockable by excess cold DOTATOC

Ex vivo quantification at 60 min

Conventional biodistribution (n=1) confirms tumor binding and high renal accumulation

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Heart Lung Liver Splen Stomach Kidney Tumor Muscle Blood

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time activity curve in tumor tissue

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Sc-44-DOTATOC

Ga-68-DOTATOC

Sc-44-DOTATOC (blocked)

Binding kinetic for 44Sc-DOTATOC is similar to 68Ga-DOTATOC

1 h 2 h 6 h 17 h

Scandium-44-DOTATOC shows normal tumor binding butblood clearance is slow and renal retention is high

KidneysTomorHeart

long term imaging with Scandium-44-DOTATOC

1 h

KidneysTumor Heart

Gallium-68-DOTATOC

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Scandium-44-DOTATOC

Comparision of PET Scans

Organ distribution of Ga-68-DOTATOC and Sc-44-

DOTATOC 1 h after injection

Conclusion:

•Scandium-44-DOTATOC (T1/2=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