Somatostatin receptor in breast cancer and axillary nodes: study with scintigraphy, histopathology and receptor autoradiography

Albérini, Jean Louis; Meunier, B.; Denzler, B.; Devillers, Anne; Tass, Patrick; Dazord, L.; Simple, T. Le; Laissue, Jean A.; Jong, R. de Josselin de; Cloirec, J. Le; Reubi, Jean Claude; Bourguet, P.

doi:10.1023/a:1006447325077

Cited by 27 publications

(28 citation statements)

References 20 publications

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“…The mean density of the receptor-positive cases is 844 6 168 dpm/mg of tissue (mean 6 SEM). These data are comparable with previously reported results (22). With 125 I-JR11, however, sst can be detected in as many as 12 of 13 breast cancers, often in high density.…”

Section: Resultssupporting

confidence: 92%

“…One group of tumors, shown previously with sst 2 agonist tracers to have low (,1,000 dpm/mg tissue) levels or a lack of sst 2 , consisting of 13 samples of breast carcinomas, 12 samples of renal cell cancers, 15 samples of NHL, 5 samples of medullary thyroid cancers, 14 samples of prostate cancers, and 17 samples of colon cancers was used in receptor autoradiography experiments as reported previously (22)(23)(24)(25)(26)(27)(28)(29). Successive sections were incubated in a buffer solution containing the standard amount of 30,000 cpm/100 mL of 125 I-Tyr 3 -octreotide or 30,000 cpm/100 mL of 125 I-JR-11.…”

Section: Resultsmentioning

confidence: 99%

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Highly Increased ¹²⁵I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst₂ Targeting in Human Cancers

et al. 2016

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There is recent in vitro and in vivo evidence that somatostatin receptor subtype 2 (sst 2 ) antagonists are better tools to target neuroendocrine tumors (NETs) than sst 2 agonists. Indeed, antagonists bind to a greater number of sst 2 sites than agonists. Whether sst 2 antagonists could be used successfully to target non-NETs, expressing low sst 2 density, is unknown. Here, we compare quantitatively 125 I-JR11 sst 2 antagonist binding in vitro with that of the sst 2 agonist 125 I-Tyr 3 -octreotide in large varieties of non-NET and NET. Methods: In vitro receptor autoradiography was performed with 125 I-JR11 and 125 I-Tyr 3 -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 sst 2 sites than 125 I-Tyr 3 -octreotide. In 13 breast cancers, 8 had a low binding (mean density, 844 6 168 dpm/mg of tissue) with the agonist whereas 12 had a high binding (mean density, 4,447 6 1,128 dpm/mg of tissue) with the antagonist. All 12 renal cell cancers showed a low binding of sst 2 with the agonist (mean density, 348 6 49 dpm/mg of tissue) whereas all cases had a high sst 2 binding with the antagonist (mean density, 3,777 6 582 dpm/mg of tissue). One of 5 medullary thyroid cancers was positive with the agonist, whereas 5 of 5 were positive with the antagonist. In 15 nonHodgkin lymphomas, many more sst 2 sites were labeled with the antagonist than with the agonist. In 14 prostate cancers, none had sst 2 binding with the agonist and only 4 had a weak binding with the antagonist. None of 17 colon cancers showed sst 2 sites with the agonist, and only 3 cases were weakly positive with the antagonist. In the various tumor types, adjacent sst 2 -expressing tissues such as vessels, lymphocytes, nerves, mucosa, or stroma were more strongly labeled 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 sst 2 sites measured with the antagonist. Conclusion: All renal cell cancers and most breast cancers, non-Hodgkin lymphomas, and medullary thyroid cancers represent novel indications for the in vivo radiopeptide targeting of sst 2 by sst 2 antagonists, comparable to NET radiotargeting with sst 2 agonists. Somat ostatin receptors (sst) are highly overexpressed in gastroenteropancreatic and extra-gastrointestinal neuroendocrine tumors (NETs). This represents the molecular basis for sst-targeted diagnostic and therapeutic procedures in NET patients with somatostatin analogs (1-3). One main clinical application makes use of the inhibitory effects of somatostatin on NET cells, particularly on hormone secretion: long-acting somatostatin analogs, such as octreotide or lanreotide, potently inhibit tumoral hormone secretion and improve related symptoms. The second targeting approach is based on the administration of radioactive somatostatin analogs for diagnostic or therapeutic purposes. Indeed, 111 In-octreotide scintigraphy (OctreoScan; Mal...

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Highly Increased ¹²⁵I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst₂ Targeting in Human Cancers

et al. 2016

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“…Of particular interest are the results in the nonneuroendocrine, nonclassic tumor targets, namely tumors that normally express a low density of receptors, such as breast carcinomas, renal cell cancers, or non-Hodgkin lymphomas (14)(15)(16)25,26). Those tumors are not currently among those being routinely investigated with 111 In-pentetreotide imaging.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of ¹⁷⁷Lu-DOTA-sst₂ Antagonist Versus ¹⁷⁷Lu-DOTA-sst₂ Agonist Binding in Human Cancers In Vitro

Cescato

Waser²,

Fani³

et al. 2011

J Nucl Med

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Somatostatin receptor targeting of neuroendocrine tumors using radiolabeled somatostatin agonists is today an established method to image and treat cancer patients. However, in a study using an animal tumor model, somatostatin receptor antagonists were shown to label sst 2 -and sst 3 -expressing tumors in vivo better than agonists, with comparable affinity even though they are not internalized into the tumor cell. In the present study, we evaluated the in vitro binding of the antagonist 177 Lu-DOTApNO 2 -Phe-c (DCys-Tyr-DTrp-Lys-Thr-Cys) DTyrNH 2 ( 177 Lu-DOTA-BASS) or the 177 Lu-DOTATATE agonist to sst 2 -expressing human tumor samples. Methods: Forty-eight sst 2 -positive human tumor tissue samples (9 ileal carcinoids, 10 pheochromocytomas, 7 breast carcinomas, 10 renal cell carcinomas, and 12 non-Hodgkin lymphomas) were analyzed by in vitro receptor autoradiography for the expression of sst 2 , comparing the binding capacity of 177 Lu-DOTA-BASS and 177 Lu-DOTATATE in successive tissue sections. The autoradiograms were quantitated using an electronic autoradiography detection system. Results: In all cases, the radiolabeled antagonist bound to more receptor sites than did the agonist. The mean ratios of the antagonist 177 Lu-DOTA-BASS to the agonist 177 Lu-DOTATATE were 4.2 6 0.5 in the 9 ileal carcinoids, 12 6 3 in the 10 pheochromocytomas, 11 6 4 in the 7 breast carcinomas, 5.1 6 0.6 in the 10 renal cell carcinomas, and 4.8 6 0.7 in the 12 non-Hodgkin lymphomas. Conclusion: The present in vitro human data, together with previous in vivo animal tumor data, are strong arguments indicating that sst 2 antagonists may be worth testing in vivo in patients in a wide range of tumors including nonneuroendocrine tumors.

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“…One critical prerequisite for successful in vivo targeting is a high receptor expression in tumors, allowing a high tumoral radiotracer accumulation (4,7). Equally important is a low receptor expression in normal tissues surrounding tumors, at sites of tumor origin and of metastasis, for receptor-targeted scintigraphy will detect tumors with adequate sensitivity only in the case of a high ratio of tumor to background signal (8,9). Moreover, knowledge of the distribution and putative functions of a peptide receptor in normal tissues is important to estimate the potential of side effects of a peptide therapy (10).…”

mentioning

confidence: 99%

GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting

Körner

Stöckli²,

Waser³

et al. 2007

Journal of Nuclear Medicine

398

303

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Peptide hormone receptors overexpressed in human tumors, such as somatostatin receptors, can be used for in vivo targeting for diagnostic and therapeutic purposes. A novel promising candidate in this field is the GLP-1 receptor, which was recently shown to be massively overexpressed in gut and lung neuroendocrine tumors-in particular, in insulinomas. Anticipating a major development of GLP-1 receptor targeting in nuclear medicine, our aim was to evaluate in vitro the GLP-1 receptor expression in a large variety of other tumors and to compare it with that in nonneoplastic tissues. Methods: The GLP-1 receptor protein expression was qualitatively and quantitatively investigated in a broad spectrum of human tumors (n 5 419) and nonneoplastic human tissues (n 5 209) with receptor autoradiography using 125 I-GLP-1(7-36)amide. Pharmacologic competition experiments were performed to provide proof of specificity of the procedure. Results: GLP-1 receptors were expressed in various endocrine tumors, with particularly high amounts in pheochromocytomas, as well as in brain tumors and embryonic tumors but not in carcinomas or lymphomas. In nonneoplastic tissues, GLP-1 receptors were present in generally low amounts in specific tissue compartments of several organs-namely, pancreas, intestine, lung, kidney, breast, and brain; no receptors were identified in lymph nodes, spleen, liver, or the adrenal gland. The rank order of potencies for receptor binding-namely, GLP-1(7-36)amide 5 exendin-4 GLP-2 5 glucagon(1-29)-provided proof of specific GLP-1 receptor identification. Conclusion: The GLP-1 receptors may represent a novel molecular target for in vivo scintigraphy and targeted radiotherapy for a variety of GLP-1 receptor-expressing tumors. For GLP-1 receptor scintigraphy, a low-background signal can be expected, on the basis of the low receptor expression in the normal tissues surrounding tumors. G protein-coupled peptide hormone receptors play an increasing role in cancer medicine. This role is based primarily on the peptide receptor overexpression on tumor cells, which allows specific receptor-targeted scintigraphic tumor imaging and tumor therapy with radiolabeled peptide analogs (1). The somatostatin receptors were the first peptide receptors identified for these purposes, and somatostatin receptor targeting has now become an integral part of the routine management of patients with gastroenteropancreatic neuroendocrine tumors. Somatostatin receptor scintigraphy (OctreoScan [ 111 In-pentetreotide]; Mallinckrodt, Inc.) detects these tumors with extremely high sensitivity and specificity (2). Moreover, recent results from clinical studies performing somatostatin receptor radionuclide therapy of these tumors are very promising (3,4).Prompted by the success of somatostatin receptor targeting, we have evaluated the overexpression of other peptide receptor families in tumors in vitro (1), with the aim, eventually, of being able to target in vivo a larger spectrum of tumors or individual tumors more efficiently with multiple pepti...

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Somatostatin receptor in breast cancer and axillary nodes: study with scintigraphy, histopathology and receptor autoradiography

Abstract: Somatostatin receptor scintigraphy does not appear to be sensitive enough to evaluate axillary node extension of breast cancer or even to confirm the presence of tumoral tissue, and this whatever the administration route for (111)In-pentetreotide.

Cited by 27 publications

References 20 publications

Highly Increased ¹²⁵I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst₂ Targeting in Human Cancers

Highly Increased ¹²⁵I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst₂ Targeting in Human Cancers

Evaluation of ¹⁷⁷Lu-DOTA-sst₂ Antagonist Versus ¹⁷⁷Lu-DOTA-sst₂ Agonist Binding in Human Cancers In Vitro

GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting

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Somatostatin receptor in breast cancer and axillary nodes: study with scintigraphy, histopathology and receptor autoradiography

Abstract: Somatostatin receptor scintigraphy does not appear to be sensitive enough to evaluate axillary node extension of breast cancer or even to confirm the presence of tumoral tissue, and this whatever the administration route for (111)In-pentetreotide.

Cited by 27 publications

References 20 publications

Highly Increased 125I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst2 Targeting in Human Cancers

Highly Increased 125I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst2 Targeting in Human Cancers

Evaluation of 177Lu-DOTA-sst2 Antagonist Versus 177Lu-DOTA-sst2 Agonist Binding in Human Cancers In Vitro

GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting

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Highly Increased ¹²⁵I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst₂ Targeting in Human Cancers

Highly Increased ¹²⁵I-JR11 Antagonist Binding In Vitro Reveals Novel Indications for sst₂ Targeting in Human Cancers

Evaluation of ¹⁷⁷Lu-DOTA-sst₂ Antagonist Versus ¹⁷⁷Lu-DOTA-sst₂ Agonist Binding in Human Cancers In Vitro