Small Animal PET-Imaging with Scandium-44-DOTATOC Matthias Miederer - - PowerPoint PPT Presentation

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Dec 26, 2022 155 likes •304 views

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 Rsch 2 Department of nuclear

SLIDE 1

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 and Institute of radiochemistry2

University Mainz, Germany

SLIDE 2

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

SLIDE 3

Correlation of dosimetry with single time point renal uptake

(111In-Octreotide measurements, calculation for 177Lu therapy)

0.5 1 1.5 2 2.5 0.5 1 1.5 2 2.5 3 3.5

number of disintegrations % of total injected activity

1 2 3 4 5 6 0.5 1 1.5 2 2.5 3 3.5

number of disintegrations % of total injected activity

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

SLIDE 4

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

Ideal for slow biological processes
Applicable for Dosimetry
Three photon imaging without

reconstruction processes might be possible

SLIDE 5

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 68Ga/44Sc

SLIDE 6

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

T air W

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

SLIDE 7

y = 0.5409x

10 20 30 40 50 60 10 20 30 40 50 60 70 80

Activity concentration (kBq/ml) PET measured activity concentration (kBq/ml)

NAC center AC 0.9 center NAC peripheral AC 0.9 peripheral Linear (NAC center)

Calibration of the PET- Scanner (250 ml phantom)

SLIDE 8

In vivo PET quantification at 60 min

10 20 30 40 50 60 tumor heart lung liver kidney muscle %ID/ml

Relative low binding, blockable by excess cold DOTATOC

SLIDE 9

Ex vivo quantification at 60 min

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

5 10 15 20 25 30 35 40 45 50

Heart Lung Liver Splen Stomach Kidney Tumor Muscle Blood

%ID/g

SLIDE 10

time activity curve in tumor tissue

20 40 60 80 100 120 140 160 180 200 10 20 30 40 50 60 70 80 90 100 time (min) activity concentration (kBq/ml)

Sc-44-DOTATOC Ga-68-DOTATOC Sc-44-DOTATOC (blocked)

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

SLIDE 11

1 h 2 h 6 h 17 h

Scandium-44-DOTATOC shows normal tumor binding but blood clearance is slow and renal retention is high Kidneys Tomor Heart long term imaging with Scandium-44-DOTATOC

SLIDE 12

1 h

Kidneys Tumor Heart Gallium-68- DOTATOC

1 h

Scandium-44- DOTATOC

Comparision of PET Scans

SLIDE 13

Organ distribution of Ga-68-DOTATOC and Sc-44- DOTATOC 1 h after injection

SLIDE 14

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