Since the introduction of somatostatin receptor (sst) imaging using 123I-Tyr3-octreotide [1], peptide receptor imaging and radiotherapy (PRRT) has become an established modality in the management of neuroendocrine tumours (NET) [2].

Based on the findings of a previous study [3] investigating metal-labelled DOTA-octreotides substituted at Tyr3, we hypothesized that derivatives of DOTA-iodo-Tyr3-octreotide might be excellent candidates for sstr imaging and therapy. Consequently, we evaluated 68Ga-DOTA-iodoTyr3-octreotate (68Ga-HA-DOTATATE; HA, high affinity) in vitro and in a preliminary PET study. As hypothesized, 68Ga-HA-DOTATATE showed high affinity for human sst2,5 as well as diagnostic and logistical advantages, i.e. unlimited precursor availability. The (Leu8,D-Trp22, [125I]Tyr25)-SST28 IC50 values (in nanomoles) for Ga-HA-DOTATATE were >10.000 (sst1), 0.64 ± 0.23 (sst2), >1,000 (sst3 and sst4) and 59.7 ± 15.1 (sst5), and for Ga-DOTATATE were >10,000 (sst1), 0.67 ± 0.25 (sst2), >1.000 (sst3), 822 ± 327 (sst4) and >1,000 (sst5).

In a first PET study a 73-year-old patient suffering from a NET with unknown primary and liver metastases was investigated with 68Ga-HA-DOTATATE and 68Ga-DOTATATE. Both agents showed a possible small primary tumour in the midgut and five liver metastases that showed somewhat higher 68Ga-HA-DOTATATE uptake (mean SUVmax 23.8 vs. 21.6). The visual detectability of three small liver metastases with low uptake was superior with 68Ga-HA-DOTATATE.

In summary, 68Ga-HA-DOTATATE provides high-quality images comparable to or better than those with 68Ga-DOTATATE. Further clinical studies are needed to confirm these first results and explore the use of HA-DOTATATE agents for PRRT.

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