Tumor uptake of 68Ga-DOTA-Tyr3-octreotate: animal PET studies of tumor flow and acute somatostatin receptor modulation in the CA20948 rat model.
BACKGROUND
Factors determining the in vivo uptake of radiolabeled somatostatin analogs by neuroendocrine tumors are poorly known. The aim is to evaluate in vivo tumor perfusion and regulation of somatostatin receptors (sstr) following acute exposure to octreotide, in an animal model of neuroendocrine tumor.


METHODS
H(2)(15)O flow studies were performed in 8 CA20948 tumor-bearing rats and another 36 rats underwent three [(68)Ga]-DOTA-Tyr(3)-octreotate imaging sessions at 24-h intervals. After baseline (Day 0) imaging, scanning was repeated on Day 1 after octreotide injection (175 microg/kg), with a variable delay: no injection (controls, n=7), coinjection (n=6), and octreotide injection 20 min (n=7), 2 h (n=8) and 4 h (n=8) before imaging. Repeat images without octreotide was performed at Day 2 followed by sacrifice and tumor counting.


RESULTS
H(2)(15)O studies failed to measure quantitative tumor perfusion in this model. On Day 1, ratio of tumor uptake to Day 0 was 1.2+/-0.3 in controls; 0.6+/-0.2 in the coinjection group; 0.9+/-0.2, 1.1+/-0.1 and 1.2+/-0.2 in the other groups, respectively. Uptake in the coinjection group showed a statistically significant reduction of tumor uptake (P<.0001). All groups showed increased uptake on Day 2, without statistical differences between groups. In vivo tumor counts showed good correlation with ex vivo countings (R(2)=0.946).


CONCLUSIONS
Acute exposure to unlabeled octreotide in this neuroendocrine tumor model results in a rapid recycling or resynthesis of sstr. Positron emission tomography (PET) allowed to reliably assess quantitative uptake of [(68)Ga]-DOTA-Tyr(3)-octreotate over time in the same animal, but failed in this model to measure tumor perfusion.
Hanin
François-Xavier
FX
Molecular Imaging and Experimental Radiotherapy Unit (MIER), Université Catholique de Louvain, B-1200 Brussels, Belgium. fx.hanin@uclouvain.be
Pauwels
Stanislas
S
Bol
Anne
A
Breeman
Wout
W
de Jong
Marion
M
Jamar
François
F
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004195:Disease Models, Animal; D005710:Gallium Radioisotopes / Q000737:chemistry; D006207:Half-Life; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D010104:Oxygen Radioisotopes / Q000737:chemistry; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism*; D015203:Reproducibility of Results; D013004:Somatostatin / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry / Q000378:metabolism
C476041:DOTA-Tyr(1)-octreotate; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D010104:Oxygen Radioisotopes; D011849:Radioactive Tracers; D017481:Receptors, Somatostatin; D014867:Water; D013004:Somatostatin; C093733:somatostatin receptor 2; D015282:Octreotide