[(99m)Tc]Demotate 2 in the detection of sst(2)-positive tumours: a preclinical comparison with [(111)In]DOTA-tate.
OBJECTIVE
The aim of this study was to evaluate [(99m)Tc]Demotate 2 ([(99m)Tc-N(4) (0-1),Asp(0),Tyr(3)]octreotate) as a candidate for in vivo imaging of sst(2)-positive tumours and to compare it with [(111)In]DOTA-tate ([(111)In-DOTA(0),Tyr(3)]octreotate).


METHODS
Labelling of Demotate 2 with (99m)Tc was performed at room temperature using SnCl(2) as reductant in the presence of citrate at alkaline pH. Radiochemical analysis involved ITLC and HPLC methods. Peptide conjugate affinities for sst(2) were determined by receptor autoradiography on rat brain cortex sections using [DOTA(0),(125)I-Tyr(3)]octreotate as the radioligand. The affinity profile of Demotate 2 for human sst(1)-sst(5) was studied by receptor autoradiography in cell preparations using the universal somatostatin radioligand [(125)I][Leu(8),(D: )Trp(22),Tyr(25)]somatostatin-28. The internalisation rates of [(99m)Tc]Demotate 2 and [(111)In]DOTA-tate were compared in sst(2)-positive and -negative control cell lines. Biodistribution of radiopeptides was studied in male Lewis rats bearing CA20948 tumours.


RESULTS
Peptide conjugates showed selectivity and a high affinity binding for sst(2) (Demotate 2 IC(50)=3.2 nM and DOTA-tate IC(50)=5.4 nM). [(99m)Tc]Demotate 2, like [(111)In]DOTA-tate, internalised rapidly in all sst(2)-positive cells tested, but not in sst(2)-negative control cells. After injection in CA20948 tumour-bearing rats both radiopeptides showed high and specific uptake in the sst(2)-positive organs and in the implanted tumour and rapid excretion from non-target tissues via the kidneys.


CONCLUSIONS
[(99m)Tc]Demotate 2, similarly to the known sst(2)-targeting agent [(111)In]DOTA-tate, showed promising biological qualities for application in the scintigraphy of sst(2)-positive tumours.
Institute of Radioisotopes, Radiodiagnostic Products, National Center for Scientific Research "Demokritos", 15310 Ag. Paraskevi Attikis, Athens, Greece. mainathe@rrp.demokritos.gr
Theodosia
T
Maina
Berthold A
BA
Nock
Paul
P
Cordopatis
Bert F
BF
Bernard
Wout A P
WA
Breeman
Arthur
A
van Gameren
Ria
R
van den Berg
Jean-Claude
JC
Reubi
Eric P
EP
Krenning
Marion
M
de Jong
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D008297:Male; D008657:Metabolic Clearance Rate; D009363:Neoplasm Proteins / Q000378:metabolism*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D017481:Receptors, Somatostatin / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
C499964:111In-octreotate, DOTA(0)-Tyr(3)-Thr(8)-; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C470035:technetium Tc 99m demotate; C093733:somatostatin receptor 2; D015282:Octreotide