Labeling, stability and biodistribution studies of 99mTc-cyclized Tyr3-octreotate derivatives

Nucl Med Biol. 2011 May;38(4):549-55. doi: 10.1016/j.nucmedbio.2010.10.006. Epub 2010 Dec 3.


Introduction: To probe the interplay between radiotracer stability and somatostatin receptor affinity, Tyr(3)-octreotate and six variations of its peptide sequence, for which the Re-cyclized products were previously reported, were radiolabeled with (99m)Tc and investigated for their in vitro stability.

Methods: Radiolabeling of the peptides was effected by ligand exchange from (99m)Tc-glucoheptonate, and the desired products were purified by radio-RP-HPLC. The in vitro stability in phosphate buffered saline, mouse serum and cysteine solutions at physiological temperature and pH for all seven (99m)Tc-cyclized peptides was determined by radio-RP-HPLC and radio-TLC. Normal CF-1 mouse biodistribution studies were performed for three of the (99m)Tc-cyclized peptides.

Results: Based on the fully characterized Re-cyclized peptide analogues, four (99m)Tc-coordination motifs were proposed for the (99m)Tc-cyclized peptides. Technetium-99m-cyclized Tyr(3)-octreotate derivatives with N(2)S(2) metal coordination modes and large metal ring sizes were susceptible to oxidation and loss of (99m)Tc in the form of (99m)TcO(4)(-), as evidenced by their instability in the various solutions under physiological conditions (15-58% intact at 24 h). As anticipated, the addition of a third cysteine to the sequence stabilized the (99m)Tc metal coordination, and peptides with NS(3) coordination modes remained >85% intact out to 24 h. No significant differences were observed in the biodistribution studies performed with three peptides of varying stabilities.

Conclusions: Improvements in stability were not sufficient to outweigh the low somatostatin receptor affinity for the peptides in this study. Further improvements in the peptide sequence and/or metal coordination are needed to result in a radiodiagnostic/radiotherapeutic pair for targeting the somatostatin receptor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Cyclization
  • Cysteine / chemistry
  • Drug Stability
  • Female
  • Isotope Labeling / methods*
  • Mice
  • Organotechnetium Compounds / chemistry*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / metabolism*
  • Peptides, Cyclic / pharmacokinetics
  • Receptors, Somatostatin / metabolism


  • Organotechnetium Compounds
  • Peptides, Cyclic
  • Receptors, Somatostatin
  • octreotate, Tyr(3)-
  • Cysteine