Lu labelling of other target specific ligands

The macrocycle l,4,7,10-tetraazacyclododecane-N,N, N ,N -tetraacetic acid (DOTA) is known to form stable complexes with lanthanides. A steroid conjugate (Fig. 8.16) was prepared via coupling of 6a-amino-17p-estradiol with a C functionalized DOTA derivative, namely, p-thiocyanatobenzyl DOTA, as a BFCA. The synthesis of 6a-amino-17p-estradiol was carried out by a four step reaction sequence. The intermediate and target compounds were characterized using high resolution H-NMR spectroscopy. 

Pictorial representation of the p-NCS-benzyl-DOTA-estradiol conjugate. 

A binding of 13.2 0.8% ( = 3) was observed with 5 x 10 MCF-7 cells for 1 gg of the Lu-p-NCS-benzyl-DOTA-estradiol complex. With SepPak purification, the cell uptake improved to 17.1 1.6% (n = 3). No further increase in cell uptake was observed with HPLC purification. It was observed that the tracer uptake in the cells decreased to 8.3 2.0% (n = 3) with the addition of 100 gg of cold estradiol. Similar results were observed when these experiments were carried out on 24 well plates where cells were plated 1 d prior to the experiments. The decrease in cell uptake with the addition of estradiol indicated the specificity of the radiolabelled conjugate for the MCF-7 cell lines. Blank experiments were carried out with Lu labelled BFCA under similar experimental conditions. No retention of the activity in the cell pellet was observed, ruling out the possibility of carrier mediated uptake. 

The metronidazole-BFCA conjugate was radiolabelled with Lu of high radiochemical purity (97%). Preliminary biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumours revealed good tumour uptake (1.30% ID/g at 30 min post-injection) with rapid renal clearance (94.48% ID at 30 min post-injection) and significant tumour to blood (28.00 at 3 h postinjection) and tumour to muscle (14.00 at 3 h post-injection) ratios. 

A polyazamacrocyclic-nitrotriazole conjugate for radiolabelling with the therapeutic radioisotope Lu was prepared. The nitroimidazole used for the 

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