TY - JOUR T1 - Small-Animal PET with a σ-Ligand, <sup>11</sup>C-SA4503, Detects Spontaneous Pituitary Tumors in Aged Rats JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1377 LP - 1383 DO - 10.2967/jnumed.112.115931 VL - 54 IS - 8 AU - Nisha K. Ramakrishnan AU - Anna A. Rybczynska AU - Anniek K.D. Visser AU - Krisztina Marosi AU - Csaba J. Nyakas AU - Chantal Kwizera AU - Jurgen W.A. Sijbesma AU - Philip H. Elsinga AU - Kiichi Ishiwata AU - Jan Pruim AU - Rudi A.J.O. Dierckx AU - Aren van Waarde Y1 - 2013/08/01 UR - http://jnm.snmjournals.org/content/54/8/1377.abstract N2 - 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. ER -