Small-Animal PET with a sigma-Ligand, C-11-SA4503, Detects Spontaneous Pituitary Tumors in Aged Rats
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Zugriff:
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 sigma-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 C-11-SA4503 C-11-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 sigma-1 agonist tracer C-11-SA4503. The time-dependent uptake of C-11 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 (V-T) of the tracer was significantly higher in the tumor than in the normal pituitary. Surprisingly, a higher V-T was also seen in the brain and thyroid tissue of animals with pituitary tumors than in healthy rats. The increase in V-T 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 (K-1/k(2)) of C-11-SA4503. The increase in V-T in the tumor on the other hand was accompanied by a significant increase in BPND. Western blotting analysis indicated that pituitary tumors overexpressed sigma-1 receptors. Conclusion: The overexpression of sigma-1 receptors in spontaneous pituitary tumors is detected as an increase in uptake and BPND of C-11-SA4503. Therefore, this tracer may have promise for the detection of pituitary adenomas, using PET.
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Small-Animal PET with a sigma-Ligand, C-11-SA4503, Detects Spontaneous Pituitary Tumors in Aged Rats
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Autor/in / Beteiligte Person: | Kuzhuppilly Ramakrishnan, Nisha ; Rybczynska, Anna A. ; Visser, Anniek K. D. ; Marosi, Krisztina ; Nyakas, Csaba J. ; Kwizera, Chantal ; Sijbesma, Jurgen W. A. ; Elsinga, Philip H. ; Ishiwata, Kiichi ; Pruim, Jan ; Dierckx, Rudi A. J. O. ; van Waarde, Aren |
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Zeitschrift: | $2, 2013, S. 1377-1383 |
Veröffentlichung: | 2013 |
Medientyp: | academicJournal |
DOI: | 10.2967/jnumed.112.115931 |
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