Small-animal PET with a s-ligand, 11C-SA4503, detects spontaneous pituitary tumors in aged rats

Nisha K. Ramakrishnan, Anna A. Rybczynska, Anniek K D Visser, Krisztina Marosi, C. Nyakas, Chantal Kwizera, Jurgen W A Sijbesma, Philip H. Elsinga, Kiichi Ishiwata, Jan Pruim, Rudi A J O Dierckx, Aren Van Waarde

Research output: Contribution to journalArticle

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Abstract

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 s-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 s-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 (K 1/k2) of 11C-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 s-1 receptors. Conclusion: The overexpression of s-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. COPYRIGHT

Original languageEnglish
Pages (from-to)1377-1383
Number of pages7
JournalJournal of Nuclear Medicine
Volume54
Issue number8
DOIs
Publication statusPublished - Aug 1 2013

Fingerprint

Pituitary Neoplasms
Ligands
Thyroid Gland
Brain Neoplasms
Brain
Neoplasms
SA 4503
Positron-Emission Tomography
Radioactivity
Wistar Rats
Western Blotting

Keywords

  • C-SA4503
  • Kinetic analysis
  • Sigma receptor
  • Small-animal PET
  • Spontaneous pituitary tumor

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Ramakrishnan, N. K., Rybczynska, A. A., Visser, A. K. D., Marosi, K., Nyakas, C., Kwizera, C., ... Van Waarde, A. (2013). Small-animal PET with a s-ligand, 11C-SA4503, detects spontaneous pituitary tumors in aged rats. Journal of Nuclear Medicine, 54(8), 1377-1383. https://doi.org/10.2967/jnumed.112.115931

Small-animal PET with a s-ligand, 11C-SA4503, detects spontaneous pituitary tumors in aged rats. / Ramakrishnan, Nisha K.; Rybczynska, Anna A.; Visser, Anniek K D; Marosi, Krisztina; Nyakas, C.; Kwizera, Chantal; Sijbesma, Jurgen W A; Elsinga, Philip H.; Ishiwata, Kiichi; Pruim, Jan; Dierckx, Rudi A J O; Van Waarde, Aren.

In: Journal of Nuclear Medicine, Vol. 54, No. 8, 01.08.2013, p. 1377-1383.

Research output: Contribution to journalArticle

Ramakrishnan, NK, Rybczynska, AA, Visser, AKD, Marosi, K, Nyakas, C, Kwizera, C, Sijbesma, JWA, Elsinga, PH, Ishiwata, K, Pruim, J, Dierckx, RAJO & Van Waarde, A 2013, 'Small-animal PET with a s-ligand, 11C-SA4503, detects spontaneous pituitary tumors in aged rats', Journal of Nuclear Medicine, vol. 54, no. 8, pp. 1377-1383. https://doi.org/10.2967/jnumed.112.115931
Ramakrishnan, Nisha K. ; Rybczynska, Anna A. ; Visser, Anniek K D ; Marosi, Krisztina ; Nyakas, C. ; Kwizera, Chantal ; Sijbesma, Jurgen W A ; Elsinga, Philip H. ; Ishiwata, Kiichi ; Pruim, Jan ; Dierckx, Rudi A J O ; Van Waarde, Aren. / Small-animal PET with a s-ligand, 11C-SA4503, detects spontaneous pituitary tumors in aged rats. In: Journal of Nuclear Medicine. 2013 ; Vol. 54, No. 8. pp. 1377-1383.
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abstract = "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 s-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 s-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 (K 1/k2) of 11C-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 s-1 receptors. Conclusion: The overexpression of s-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. COPYRIGHT",
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AU - Nyakas, C.

AU - Kwizera, Chantal

AU - Sijbesma, Jurgen W A

AU - Elsinga, Philip H.

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