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?

AIM: 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.

Improved column-based radiochemical processing of the generator produced 68Ga.

An improved chemical strategy for processing of the generator produced (68)Ga was developed based on processing of the original (68)Ge/(68)Ga generator eluate on a micro-column. Direct pre-concentration and purification of the eluted (68)Ga is performed on a cation-exchange resin in hydrochloric acid/acetone media. A supplementary step based on a second micro-column filled with a second resin allows direct re-adsorption of (68)Ga eluted from the cation exchanger. (68)Ga is finally striped from the second resin with a small volume of pure water. For this purpose a strong anion exchanger and a novel extraction chromatographic resin based on tetraalkyldiglycolamides are characterized. The strategy allows online pre-concentration and purification of (68)Ga from the original generator eluate. The supplementary column allows transferring (68)Ga with high radionuclide and chemical quality in the aqueous solution with small volume and low acidity useful for direct radiolabeling reactions.

Post-elution processing of (44)Ti/(44)Sc generator-derived (44)Sc for clinical application.

The (44)Ti/(44)Sc (T(1/2)(44)Ti=60a) generator provides cyclotron-independent access to positron-emitting (44)Sc (T(1/2)=3.97d) for PET imaging. This work aims to post-elution processing of initial (44)Sc generator eluates in order to reduce its volume, HCl concentration and remove the oxalate anions. The on-line adsorption of (44)Sc on cationic resin AG 50W-X8 (200-400 mesh, H(+)-form) is achieved with >98% efficacy. Subsequently, the purified (44)Sc is desorbed by using 3ml of 0.25M ammonium acetate (pH=4.0). The post-processing takes 10min. The overall yield of the post-processing reached 90%, which is referred to the (44)Sc obtained from the (44)Ti/(44)Sc generator. In addition to the chemical purification, the content of (44)Ti breakthrough was further reduced by one order of magnitude. The 185MBq generator finally provides 150MBq of (44)Sc containing <10Bq of (44)Ti ready for labeling.