title: 44Sc-DOTA-BN[2-14]NH2 in comparison to 68Ga-DOTA-BN[2-14]NH2 in pre-clinical investigation. Is 44Sc a potential radionuclide for PET?
abstract: OBJECTIVE
  In the present study we demonstrate the in vitro and in vivo comparison of the (44)Sc and (68)Ga labeled DOTA-BN[2-14]NH(2). (44)Sc is a positron emitter with a half life of 3.92 h. Hence it could be used for PET imaging with ligands requiring longer observation time than in the case of (68)Ga.
  
  
  METHODS
  The binding affinity of (nat)Sc-DOTA-BN[2-14]NH(2) and (nat)Ga-DOTA-BN[2-14]NH(2) to GRP receptors was studied in competition to [(125)I-Tyr(4)]-Bombesin in the human prostate cancer cell line PC-3. A preliminary biodistribution in normal rats was performed, while first microPET images were assessed in male Copenhagen rats bearing the androgen-independent Dunning R-3327-AT-1 prostate cancer tumor.
  
  
  RESULTS
  The affinity to GRP receptors in the PC-3 cell line was higher for (nat)Ga-DOTA-BN[2-14]NH(2) (IC(50)(nM)=0.85 ± 0.06) than that of (nat)Sc-DOTA-BN[2-14]NH(2) (IC(50) (nM)=6.49 ± 0.13). The internalization rate of (68)Ga labeled DOTA-BN[2-14]NH(2) was slower than that of (44)Sc, but their final internalization percents were comparable. (68)Ga-DOTA-BN[2-14]NH(2) was externalized faster than (44)Sc-DOTA-BN[2-14]NH(2). The biodistribution of (44)Sc-DOTA-BN[2-14]NH(2) and (68)Ga-DOTA-BN[2-14]NH(2) in normal rats revealed a higher uptake in target organs and tissues of the first one while both excreted mainly through urinary tract. In microPET images both tracers were accumulated in the tumor with similar uptake patterns.
  
  
  CONCLUSIONS
  Despite the differences in the receptor affinity both the (68)Ga- and the (44)Sc-labeled DOTA-BN[2-14]NH(2) tracers showed comparable distribution and similar time constants of uptake and elimination. Moreover no differences in tumor accumulation (neither in the overall uptake nor in the dynamics) were observed from the microPet imaging. From that perspective the use of either (44)Sc or (68)Ga for detecting tumors with GRP receptors is equivalent.
authors.affiliation: National Center for Nuclear Research, Radioisotope Centre POLATOM, Otwock, Poland. eftychia.koumarianou@duke.edu
authors.forename: E
authors.initials: E
authors.lastname: Koumarianou
authors.forename: N S
authors.initials: NS
authors.lastname: Loktionova
authors.forename: M
authors.initials: M
authors.lastname: Fellner
authors.forename: F
authors.initials: F
authors.lastname: Roesch
authors.forename: O
authors.initials: O
authors.lastname: Thews
authors.forename: D
authors.initials: D
authors.lastname: Pawlak
authors.forename: S C
authors.initials: SC
authors.lastname: Archimandritis
authors.forename: R
authors.initials: R
authors.lastname: Mikolajczak
mesh_terms: D000818:Animals; D001839:Bombesin; D045744:Cell Line, Tumor; D005710:Gallium Radioisotopes; D019886:Gastrin-Releasing Peptide; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D051381:Rats; D012538:Scandium; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D019886:Gastrin-Releasing Peptide; D001839:Bombesin; D012538:Scandium