Biological characterisation of [67Ga] or [68Ga] labelled DFO-octreotide (SDZ 216-927) for PET studies of somatostatin receptor positive tumors.
Radiolabelled analogues of Somatostatin (SRIF) were demonstrated to be useful for conventional gamma-camera imaging of SRIF receptor-positive tumors and their metastases. To evaluate the feasibility of positron emission tomography (PET) or SRIF receptor-positive tumors deferoxamine (DFO) was conjugated to octreotide via a succinyl linker to form a stable conjugate with the gallium isotopes 67Ga and 68Ga. This new octreotide analog, SDZ 216-927, binds specifically and with high affinity to SRIF receptors in vitro (pKi = 8.94 +/- 0.06) and exhibits SRIF like biological properties as demonstrated by the inhibition of growth hormone (GH) release from cultured pituitary cells. SDZ 216-927 was efficiently labelled with 67Ga without affecting high affinity binding to SRIF receptors. Biodistribution studies revealed that [67Ga]SDZ 216-927 was stable in vivo and rapidly cleared from the circulation, as indicated by the low amount of 67Ga detected in the blood four hours post injection (p.i.). SRIF receptor-positive tumors were clearly visualized 10 minutes p.i. in tumor bearing rats. The specificity of ligand binding in vivo was demonstrated i) by the high tumor/non-tumor ratio 4 hours p.i. (tumor/blood 22.3:1, tumor/muscle 64.5:1, tumor/liver 4.0:1, tumor/spleen 16.8:1) and ii) by a significantly lower uptake of radioactivity in the tumor after pretreatment of tumor bearing animals with an excess of unlabelled SDZ 216-927. SDZ 216-927, when labelled with the positron emitting isotope 68Ga, clearly imaged SRIF receptor-positive tumors using positron emission tomography (PET). Therefore quantitative SRIF receptor imaging with PET seems to be possible using this new radiopharmaceutical.
Stolz
B
B
SANDOZ Pharma, Preclinical Research, Basel.
Smith-Jones
P M
PM
Albert
R
R
Reist
H
H
Mäcke
H
H
Bruns
C
C
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003676:Deferoxamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes; D066298:In Vitro Techniques; D015282:Octreotide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging; D051381:Rats; D017481:Receptors, Somatostatin / Q000032:analysis*; D014055:Tomography, Emission-Computed
D002352:Carrier Proteins; D005710:Gallium Radioisotopes; D017481:Receptors, Somatostatin; C082116:desferrioxamine B-succinyl-phenylalanine(1)-octreotide; D003676:Deferoxamine; D015282:Octreotide