Localization of Small‐cell Lung Cancer Xenografts with Iodine‐125‐, Indium‐111‐, and Rhenium‐188‐Somatostatin Analogs

Hosono, Makoto; Hosono, Masamichi; Haberberger, Thomas; Zamora, Paul O.; Guhlke, Stefan; Knapp, F. F.; Biersack, H.-J.

doi:10.1111/j.1349-7006.1996.tb02131.x

Cited by 16 publications

(12 citation statements)

References 14 publications

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“…A major limitation in NET research is the lack of robust orthotopic or patient-derived xenograft animal models that accurately represent human disease. For further agent evaluation, we selected NCI-H69 cells, which are known to endogenously express moderate to low levels of SSTR2 (15) and have been widely used for assessment of SSTR2-targeted agents (16)(17)(18)(19)(20). As anticipated, in vitro results demonstrated specific binding and internalization in NCI-H69 cells ( Supplementary Figs.…”

Section: In Vivo Imagingmentioning

confidence: 86%

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Vargas

Kossatz

Voss

et al. 2019

Clinical Cancer Research

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Purpose: Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS). Experimental Design: A multimodality chelator (MMC) was used as a "radioactive linker" to synthesize the fluorescently labeled somatostatin analog, 67/68 Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso-and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs. Results: Direct labeling with 67 Ga/ 68 Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings. Conclusions: The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.

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Section: In Vivo Imagingmentioning

confidence: 86%

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Vargas

Kossatz

Voss

et al. 2019

Clinical Cancer Research

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“…Recently, preliminary animal experiments with an octadentate octreotide derivative labelled with 90y showed promising results with respect to in vivo stability as well as inhibition of tum0ur growth [31 ]. Furthermore, somatostatin analogues have been coupled successfully with rhenium-188 using a 188W/188Re generator and routine kit coupling, although metabolic properties (hepatobiliary clearance and low tumour to normal tissue ratios) will limit their use in humans [32,33]. Other therapeutic radiometals suitable for one-step radionuclide coupling, such as terbium-161 (included in the DTPA group), are not yet generally available.…”

Section: Direct Radiolabelling Of Chelator-coniugated Peptides With Rmentioning

confidence: 99%

Iodine-131 labelled octreotide: not an option for somatostatin receptor therapy

et al. 1996

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Gamma-emitting radiopeptides are useful for scintigraphy of tumours on the basis of receptor binding. Likewise, beta-emitting radiopeptides may be used in radionuclide therapy of such tumours. As iodine-131 suggested to be suitable for this purpose, experiments were performed using three somatostatin analogues, in which the effects of coupling of a therapeutic dose of 131I to such peptides were investigated. This study deals with the radioiodination of very small amounts of peptide on a therapeutic scale, the required purification procedures after radioiodination, and the influence of high beta fluxes from 131I on a peptide during radioiodination and purification. Based on the regularly used therapeutic doses of 131I in cancer treatment and our previous experience with [111In-DTPA-D-Phe1]-octreotide, it was assumed that a minimal effective therapeutic dose of 3.7 GBq 131I has to be coupled to a maximum of approximately 100 microg peptide, representing only a slight excess of peptide over 131I. This contrasts with non-peptide radiopharmaceuticals in which high compound to radionuclide ratios are usually used. Labelling at low peptide to radionuclide ratios (low labelling yields) results in the formation of di-iodinated compounds, whereas at high peptide to radionuclide ratios (high labelling yields) mono-iodinated products of low specific activity are formed. Thus, after radioiodination the desired mono-iodinated peptide has to be separated from unreacted iodide, and from di-iodinated and unreacted peptide, as both compounds compete for the receptors. Possible radiolysis of the peptide during labelling and separation steps were investigated by irradiating 30 microgram unlabelled peptide with 370 MBq 131I in a small volume. The peptide composition of the incubation mixtures was investigated by high-performance liquid chromatography after irradiation for 30 min to 24 h. The results showed that the peptide was degraded with a half-life of less than 1 h. During the preparation of a real therapeutic dose (at much higher beta-flux) the peptide will be degraded even faster during the various steps required. In conclusion, intact mono-iodinated 131I-labelled somatostatin analogues for peptide receptor therapy will be difficult to obtain.

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“…188 Re, a potential radiotherapeutic isotope, has been coupled to octreotide. [ 188 Re]octreotide has been assessed for the in vivo localization of NCI-H69 SCLC tumor xenografts in athymic nude mice and proved as efficient as [ 111 In]pentetreotide in this regard [115]. Likewise, l6l Tb has been coupled to octreotide.…”

Section: Radiotherapeuticsmentioning

confidence: 99%

Somatostatin, Its Receptors and Analogs, in Lung Cancer

et al. 2001

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Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201–995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1–5. Although elevated plasma somatostatin levels may be detected in 14–15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [¹¹¹In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer.

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Localization of Small‐cell Lung Cancer Xenografts with Iodine‐125‐, Indium‐111‐, and Rhenium‐188‐Somatostatin Analogs

Cited by 16 publications

References 14 publications

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Iodine-131 labelled octreotide: not an option for somatostatin receptor therapy

Somatostatin, Its Receptors and Analogs, in Lung Cancer

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