Antitumor and Antiangiogenic Effects of Somatostatin Receptor-Targeted in Situ Radiation with 111In-DTPA-JIC 2DL

Güleç, Seza A.; Drouant, George J.; Fuselier, Joseph A.; Anthony, Catherine T.; Heneghan, James B.; Delcarpio, Joseph B.; Coy, David H.; Murphy, William A.; Woltering, Eugene A.

doi:10.1006/jsre.2001.6149

Cited by 25 publications

(13 citation statements)

References 14 publications

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“…Progressive internalization with increasing time, increasing dose, or their product implies increased retention time in the tumor. We have previously demonstrated that we can effectively destroy human angiogenic blood vessels with 111 Inradionuclides [16,23] [16]. This dose is in agreement with the amount of Ci-Hr required to induce high (greater than 90%) levels of cytotoxicity in the assays reported here.…”

Section: Discussionsupporting

confidence: 87%

“…This dose is in agreement with the amount of Ci-Hr required to induce high (greater than 90%) levels of cytotoxicity in the assays reported here. In the Gulec study, tumors that did not possess sst 2 in their cells were unaffected by this level of radiation, while their angiogenic response was still effectively ablated [16]. Similar cytotoxicity has been reported with angiogenic blood vessels derived from normal placental vein disks embedded in the threedimensional fibrin-thrombin clot assay [23].…”

Section: Discussionsupporting

confidence: 54%

“…Prolonged (24 -48 h) exposure of somatostatin receptorexpressing cells to iodine or indium-labeled somatostatin analogs leads to progressive increases in whole cell binding, internalization, and receptor-dependent nuclear transport of the radioligand [12]. Exposure of somatostatin receptor-expressing cells to Augeremitting radiolabeled somatostatin analogs also induces dose-dependent/receptor-dependent cytotoxicity both in vitro and in vivo [13][14][15][16]. These observations have led us to investigate the relative contribution of radioligand concentration and radioligand exposure time on binding, internalization, and cytotoxicity in somatostatin receptor-expressing cells.…”

Section: Introductionmentioning

confidence: 99%

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The effect of drug dose and drug exposure time on the binding, internalization, and cytotoxicity of radiolabeled somatostatin analogs

Anthony

Hughey

Lyons

et al. 2004

Journal of Surgical Research

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

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The effect of drug dose and drug exposure time on the binding, internalization, and cytotoxicity of radiolabeled somatostatin analogs

Anthony

Hughey

Lyons

et al. 2004

Journal of Surgical Research

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“…The human small cell lung cancer (SCLC) cell line NCI-H69, the human non-small cell lung cancer (NSCLC) cell line A549, the human breast carcinoma cell line MDA-MB-231, and the human pancreatic carcinoma cell line CAPAN-1 were all obtained from the American Type Culture Collection. The NCI-H69 (26) and MDA-MB-231 (27) cell lines overexpress the SST2r, whereas the A549 and CAPAN-1 cell lines do not express this receptor (28). Tumors from these cell lines were induced in CB/17 SCID mice.…”

Section: Methodsmentioning

confidence: 99%

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

Starkey¹,

Rebane

Drobizhev³

et al. 2008

Clinical Cancer Research

227

189

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Purpose: The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation on normal tissues and characterized the response of xenograft tumors to our PDT protocols. Experimental Design: Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon activated PDT. Results:Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal, changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation. Conclusions: These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was consistent with known responses to singlephoton activated PDT. Experiments in larger animals are warranted to determine the maximal achievable depth of treatment.Photodynamic therapy (PDT; ref. 1) is a protocol that uses light of the appropriate wavelength to activate photosensitizer accumulated in tumor tissue to its triplet state (2). The triplet excitation energy can be effectively transferred to molecular oxygen, resulting in the generation of singlet oxygen, superoxide radical, and other active oxygen species (2, 3). The singlet oxygen causes direct chemical damage to tumor and/or tumor endothelial cells (4), initiates a neutrophilic inflammatory response (5), and can stimulate both innate and specific antitumor immune responses (6 -8). Singlet-oxygen production, however, requires a sufficiently high energy of the triplet state of the sensitizer. Long-wavelength near-IR (NIR) light k ex > 750 nm has relatively low-photon energy, which restricts the range of processes that can be activated by one-photon excitation. The relation between the wavelength and the minimum excitation energy of singlet oxygen is shown in Fig. 1A. The dark gray shaded area corresponds to the excitation energy below the required minimum value, E so < 1.5 -1.6 eV (9, 10), which shows that sensitization by one-photon absorption (1PA) fails in the phototherapeutic window 780 to 950 nm, where tissues have maximum transparency to light. Sensitization by simultaneous two-photon absorption (2PA; ref. 11) combines the energy of two photons and can provide suffi...

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“…In partial contrast with these findings, other studies reported that sst2-Rs were expressed in the proliferating angiogenic sprouts of human vascular endothelium, but not in quiescent ECs. They were present at high density in proliferating blood vessels of tumors (Watson et al, 2001) and could represent an elective target in antineoplastic therapy (Gulec et al, 2001). There is proof that the sst2-R-mediated antiangiogenic action of somatostatin could either be direct, involving the inhibition of EC proliferation (Danesi et al, 1997), or indirect, being mediated by the suppression of production of growth factors, including VEGF (Cascinu et al, 2001;Mentlein et al, 2001).…”

Section: A Somatostatinmentioning

confidence: 99%

Nonclassic Endogenous Novel Regulators of Angiogenesis

Ribatti

Conconi²,

Nussdorfer³

2007

Pharmacol Rev

162

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Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor ( VEGF) and fibroblast growth factor-2 (FGF- 2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro pro-angiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG- II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide- Y, vasoactive intestinal peptide ( VIP), pituitary adenylate cyclase- activating polypeptide ( PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF ( ANG- II, ETs, PAMP, resistin, VIP and PACAP) and/ or FGF-2 systems ( PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF- 2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis

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Antitumor and Antiangiogenic Effects of Somatostatin Receptor-Targeted in Situ Radiation with 111In-DTPA-JIC 2DL

Cited by 25 publications

References 14 publications

The effect of drug dose and drug exposure time on the binding, internalization, and cytotoxicity of radiolabeled somatostatin analogs

The effect of drug dose and drug exposure time on the binding, internalization, and cytotoxicity of radiolabeled somatostatin analogs

New Two-Photon Activated Photodynamic Therapy Sensitizers Induce Xenograft Tumor Regressions after Near-IR Laser Treatment through the Body of the Host Mouse

Nonclassic Endogenous Novel Regulators of Angiogenesis

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