HIGHLY INCREASED 125I-JR11 ANTAGONIST BINDING IN VITRO REVEALS NOVEL INDICATIONS FOR SST2 TARGETING IN HUMAN CANCERS.

Reubi, Jean Claude; Waser, Beatrice; Maecke, Helmut R; Rivier, Jean E (2016). HIGHLY INCREASED 125I-JR11 ANTAGONIST BINDING IN VITRO REVEALS NOVEL INDICATIONS FOR SST2 TARGETING IN HUMAN CANCERS. Journal of nuclear medicine, 58(2), pp. 300-306. Society of Nuclear Medicine 10.2967/jnumed.116.177733

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There is recent in vitro and in vivo evidence that somatostatin receptor sst2 antagonists are better tools to target neuroendocrine tumors (NET) than sst2 agonists. Indeed, antagonists bind to a greater number of sst2 sites than agonists. Whether sst2 antagonists could be used successfully to target non-NET tumors, expressing low sst2 density, is unknown. Here, we compare quantitatively (125)I-JR11 sst2 antagonist binding in vitro with that of the sst2 agonist (125)I-Tyr3-octreotide in large varieties of non-NET and NET.

METHODS

In vitro receptor autoradiography was performed with (125)I-JR11 and (125)I-Tyr3-octreotide in cancers from prostate, breast, colon, kidney, thyroid, and lymphoid tissues, as well as NETs as reference.

RESULTS

In general, (125)I-JR11 binds to many more sst2 sites than (125)I-Tyr3-octreotide. In 13 breast cancers, 8 have low binding (mean density: 844±168 dpm/mg tissue) with the agonist while 12 have a high binding (mean density: 4447±1128 dpm/mg tissue) with the antagonist. All 12 renal cell cancers (RCC) show a low binding of sst2 with the agonist (mean density: 348±49 dpm/mg tissue) while all cases have a very high sst2 binding with the antagonist (mean density: 3777±582 dpm/mg tissue). 1/5 medullary thyroid cancers are positive with the agonist, while 5/5 are positive with the antagonist. In 15 Non-Hodgkin lymphomas (NHL), many more sst2 sites are labelled with the antagonist than with the agonist. In 14 prostate cancers, none have sst2 binding with the agonist and only 4 have a weak binding with the antagonist. None of 17 colon cancers show sst2 sites with the agonist and only 3 cases are weakly positive with the antagonist. In the various tumor types, adjacent sst2-expressing tissues such as vessels, lymphocytes, nerves, mucosa or stroma were more strongly labelled with the antagonist than with the agonist. The reference NET cases, incubated with a smaller amount of tracer, were also found to have many more sst2 sites measured with the antagonist.

CONCLUSION

All RCC, a majority of breast cancers, NHL and medullary thyroid cancers represent novel indications for the in vivo radiopeptide targeting of sst2 by sst2 antagonists, comparable to NET radiotargeting with sst2 agonists.

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