Peptide Receptor Chemoradionuclide Therapy in Small Cell Carcinoma: from Bench to Bedside

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2014 Aug 16

PMID 25125202

Citations 12

Authors

Jeremy Lewin

Carleen Cullinane

Tim Akhurst

Kelly Waldeck

D Neil Watkins

Aparna Rao

Peter Eu

Linda Mileshkin

Rodney J Hicks

Affiliations

Soon will be listed here.

Abstract

Purpose: Small cell cancers (SmCC), whether pulmonary (SCLC) or extrapulmonary, have a poor prognosis unless localised at diagnosis. Given a proportion of these cancers express somatostatin receptor subtype 2 (SSTR2), we aimed to investigate the efficacy of targeted peptide receptor chemoradionuclide therapy (PRCRT).

Methods: In this preclinical study, we used a SCLC xenograft mouse model with high expression of SSTR2 to investigate the effect of peptide receptor radionuclide therapy (PRRT) with chemotherapy compared to either alone. We subsequently explored the clinical utility in a patient with SmCC with high SSTR expression treated with PRCRT.

Results: Robust expression of SSTR2 in NCI-H69 SCLC xenografts was documented by (68)Ga-DOTA-octreotate (GaTate) (tumour to background uptake ratio = 35). The combination of PRRT using (177)Lu-DOTA-octreotate (LuTate) with carboplatin/etoposide (C/E) chemotherapy was more effective than either LuTate or C/E alone for regression of the NCI-H69 model (p value < 0.05). PRCRT was associated with significantly prolonged survival versus PRRT (p value = 0.0001) or chemotherapy alone (p value = 0.0058). In the subsequent case study, a patient with relapsed SmCC with high SSTR2 expression on GaTate PET underwent PRCRT with radiosensitising etoposide with evidence of a complete metabolic response for 4 months.

Conclusion: Given the limited treatment options in this setting, PRCRT is a promising therapeutic option for SSTR2-expressing SmCC.

Citing Articles

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Waldeck K, Van Zuylekom J, Cullinane C, Gulati T, Simpson K, Tothill R Theranostics. 2023; 13(14):4745-4761.

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Radionuclide-based theranostics - a promising strategy for lung cancer.

Zhu T, Hsu J, Guo J, Chen W, Cai W, Wang K Eur J Nucl Med Mol Imaging. 2023; 50(8):2353-2374.

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Molecular imaging phenotyping for selecting and monitoring radioligand therapy of neuroendocrine neoplasms.

Iravani A, Parihar A, Akhurst T, Hicks R Cancer Imaging. 2022; 22(1):25.

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The Current Role of Peptide Receptor Radionuclide Therapy in Meningiomas.

Fodi C, Schittenhelm J, Honegger J, Castaneda-Vega S, Behling F J Clin Med. 2022; 11(9).

PMID: 35566491 PMC: 9104797. DOI: 10.3390/jcm11092364.

Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides-Where Are We Now.

Naik M, Al-Nahhas A, Khan S Cancers (Basel). 2022; 14(3).

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