PET-pharmacokinetics of F-18-octreotide: A comparison with Ga-67-DFO- and Y-86-DTPA-octreotide

The quantitative uptake kinetics of (2-[(18)]fluoropropionyl-(D)phe(1))-octreotide (I), a somatostatin (SRIF) receptor-specific tracer, was measured by PET. Conventional organ biodistribution and in vivo stabilities of the tracer as well as in vivo displacement and SRIF receptor blocking were determined. The F-18-fluorinated octreotide was compared with ([Ga-67]-DFO-B-succinyl-(D)phe(1))-octreotide (II) and ([Y-86]-DTPA-(D)phe(1))-octreotide (III), Initially, 2-10 MBq of the labeled tracers were injected into male Lewis rats bearing an exocrine pancreatic islet cell tumor. PET measurements were performed dynamically between 0 and 120 min postinjection. Organ distributions were determined 5, 15, 30, 60, and 120 min postinjection. The extent of metabolic degradation was analyzed in serial blood and urine samples as well as in homogenised samples of tumor, liver, and kidney. The uptake of (I) by the tumor was rapid (maximum accumulation at 1-2 min postinjection) and high (about 0.5 +/- 0.2 %ID/g), followed by a fast and continuous release with k(off) = 10 +/- 2 . 10(-5) s(-1). The tracer was found to remain intact in vivo up to 120 min postinjection. Specific binding of (I) to SRIF receptors in the adrenals, the pancreas, and the pituitary gland was demonstrated in vivo by pretreatment and displacement experiments. Compound (II) also showed a fast uptake by the tumor. Its tumor residence half-life was longer (k(off) = 3.0 +/- 0.5 . 10(-5) s(-1)). Compound (II) was also predominantly excreted intact. One hour postinjection, the remaining activity in the blood pool was found to be bound to serum proteins, Early uptake kinetics for compound (III) were also rapid but reached only half the tumor uptake of (II). Compared to (I), the release of Y-86-activity from the tumor was slower (k(off) = 3.1 +/- 1.3 . 10(-5) s(-1)). Compared to (II), compound (III) was considerably less stable in vivo, The main critical organs for (II) and (III) are kidneys and bones, whereas (I) is predominantly accumulated in the liver. The in vivo behavior of (I) closely resembles C-14 labeled octreotide. Thus, (18)-labeled octreotide may be of interest in the quantitation and investigation of in vivo properties of somatostatin receptors by PET. However, the short residence of (2-[F-18]fluoropropionyl-(D)phe(1))-octreotide in tumors and its hepatobiliary excretion may complicate the interpretation of abdominal tumors. (C) 1997 Elsevier Science Inc.