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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Reubi-Kattenbusch, Jean-Claude and Waser, Beatrice

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0161-5505

Publisher:

Society of Nuclear Medicine

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

18 Jan 2017 13:29

Last Modified:

17 Oct 2019 11:06

Publisher DOI:

10.2967/jnumed.116.177733

PubMed ID:

27561878

Uncontrolled Keywords:

Autoradiography Neuroendocrine Peptides Somatostatin sst2 receptors breast cancer cancer radiopeptide targeting renal cell cancer sst2 antagonist

BORIS DOI:

10.7892/boris.92923

URI:

https://boris.unibe.ch/id/eprint/92923

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