초록
<P>Aiming to expand the application of the SST<SUB>2</SUB>R-antagonist LM4 (DPhe-c[DCys-4Pal-DAph(Cbm)-Lys-Thr-Cys]-DTyr-NH<SUB>2</SUB>) beyond [<SUP>68</SUP>Ga]Ga-DATA<SUP>5m</SUP>-LM4 PET/CT (DATA<SUP>5m</SUP>, (6-pentanoic acid)-6-(amino)methy-1,4-diazepinetriacetate), we now introduce AAZTA<SUP>5</SUP>-LM4 (AAZTA<SUP>5</SUP>, 1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)]amino-6-[pentanoic-acid]perhydro-1,4-diazepine), allowing for the convenient coordination of trivalent radiometals of clinical interest, such as In-111 (for SPECT/CT) or Lu-177 (for radionuclide therapy). After labeling, the preclinical profiles of [<SUP>111</SUP>In]In-AAZTA<SUP>5</SUP>-LM4 and [<SUP>177</SUP>Lu]Lu-AAZTA<SUP>5</SUP>-LM4 were compared in HEK293-SST<SUB>2</SUB>R cells and double HEK293-SST<SUB>2</SUB>R/wtHEK293 tumor-bearing mice using [<SUP>111</SUP>In]In-DOTA-LM3 and [<SUP>177</SUP>Lu]Lu-DOTA-LM3 as references. The biodistribution of [<SUP>177</SUP>Lu]Lu-AAZTA<SUP>5</SUP>-LM4 was additionally studied for the first time in a NET patient. Both [<SUP>111</SUP>In]In-AAZTA<SUP>5</SUP>-LM4 and [<SUP>177</SUP>Lu]Lu-AAZTA<SUP>5</SUP>-LM4 displayed high and selective targeting of the HEK293-SST<SUB>2</SUB>R tumors in mice and fast background clearance via the kidneys and the urinary system. This pattern was reproduced for [<SUP>177</SUP>Lu]Lu-AAZTA<SUP>5</SUP>-LM4 in the patient according to SPECT/CT results in a monitoring time span of 4–72 h pi. In view of the above, we may conclude that [<SUP>177</SUP>Lu]Lu-AAZTA<SUP>5</SUP>-LM4 shows promise as a therapeutic radiopharmaceutical candidate for SST<SUB>2</SUB>R-expressing human NETs, based on previous [<SUP>68</SUP>Ga]Ga-DATA<SUP>5m</SUP>-LM4 PET/CT, but further studies are needed to fully assess its clinical value. Furthermore, [<SUP>111</SUP>In]In-AAZTA<SUP>5</SUP>-LM4 SPECT/CT may represent a legitimate alternative diagnostic option in cases where PET/CT is not available.</P>