RT Journal Article SR Electronic T1 Small-Animal PET with a σ-Ligand, 11C-SA4503, Detects Spontaneous Pituitary Tumors in Aged Rats JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1377 OP 1383 DO 10.2967/jnumed.112.115931 VO 54 IS 8 A1 Nisha K. Ramakrishnan A1 Anna A. Rybczynska A1 Anniek K.D. Visser A1 Krisztina Marosi A1 Csaba J. Nyakas A1 Chantal Kwizera A1 Jurgen W.A. Sijbesma A1 Philip H. Elsinga A1 Kiichi Ishiwata A1 Jan Pruim A1 Rudi A.J.O. Dierckx A1 Aren van Waarde YR 2013 UL http://jnm.snmjournals.org/content/54/8/1377.abstract AB Pituitary tumors are often detected only after death or at late stages of the disease when they are macroadenomas with a low surgical cure rate. Spontaneous pituitary tumors occur in rats over 1 y of age. In an ongoing study of changes in σ-1 agonist binding related to aging, several of our rats developed such tumors. The aim of the current study was to assess the kinetics of 11C-SA4503 (11C-labeled 1-[2-(3,4-dimethoxyphenthyl)]-4-(3-phenylpropyl)-piperazine dihydrochloride) in tumor and brain and to evaluate the utility of this tracer in the detection of pituitary tumors. Methods: Small-animal PET scans of the brain region of male Wistar Hannover rats (age, 18–32 mo) were acquired using the σ-1 agonist tracer 11C-SA4503. The time-dependent uptake of 11C in the entire brain, tumor or normal pituitary, and thyroid was measured. A 2-tissue-compartment model was fitted to the PET data, using metabolite-corrected plasma radioactivity as the input function. Results: Pituitary tumors showed up as bright hot spots in the scans. The total distribution volume (VT) of the tracer was significantly higher in the tumor than in the normal pituitary. Surprisingly, a higher VT was also seen in the brain and thyroid tissue of animals with pituitary tumors than in healthy rats. The increase in VT in the brain and thyroid was not related to a change in nondisplaceable binding potential (BPND) but rather to an increase in the partition coefficient (K1/k2) of 11C-SA4503. The increase in VT in the tumor on the other hand was accompanied by a significant increase in BPND. Western blotting analysis indicated that pituitary tumors overexpressed σ-1 receptors. Conclusion: The overexpression of σ-1 receptors in spontaneous pituitary tumors is detected as an increase in uptake and BPND of 11C-SA4503. Therefore, this tracer may have promise for the detection of pituitary adenomas, using PET.