Targeted Radionuclide Therapy of Human Tumors

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Abstract

Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

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Most cited references 90

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Radiotherapy and immunogenic cell death.

Encouse B Golden, Lionel Apetoh (2015)

Advances in understanding the mechanisms that underlie the interplay between radiation-invoked immune responses and tumor regression are underway. Emerging applications of local radiotherapy as an immunologic adjuvant have provided radiation oncologists with a method for converting malignant cells into endogenous anticancer vaccines. The dispersion of radiotherapy-induced immune-stimulating tumor antigens released from dying tumor cells into the surrounding milieu (known as immunogenic cell death, Fig. 1), is one such exploitable process that contributes to the propagation of antitumor immunity. Downstream components of the immune system may suppress, promote, or ambiguously affect antitumoral responses. Additionally, host, tumor, and treatment-related characteristics govern the significance of these signals, thereby dictating therapeutic outcomes. Herein, we review the process of radiotherapy-induced immunogenic cell death and its role in generating an in situ vaccine to help refine radioimmunotherapy-based protocols.

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Cloning and characterization of the thyroid iodide transporter.

J-G Dai, N Carrasco, O Levy (1996)

Iodide (I-) is an essential constituent of the thyroid hormones T3 and T4, and is accumulated by the thyroid. The transport of iodide, the first step in thyroid hormogenesis, is catalysed by the Na+/I- symporter, an intrinsic membrane protein that is crucial for the evaluation, diagnosis and treatment of thyroid disorders. Although several other important thyroid proteins involved in hormogenesis have been characterized, the Na+/I- symporter has not. Here we report the isolation of a complementary DNA clone that encodes this symporter, as a result of functional screening of a cDNA library from a rat thyroid-derived cell line (FRTL-5) in Xenopus laevis oocytes. Oocyte microinjection of an RNA transcript made in vitro from this cDNA clone elicited a more than 700-fold increase in perchlorate-sensitive Na+/I- symport activity over background. To our knowledge, this is the first iodide-transporting molecule to have its cDNA cloned, providing a missing link in the thyroid hormone biosynthetic pathway.

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Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer.

Scott Tagawa, Neeta Taskar, Shankar Vallabhajosula … (2013)

To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; (177)Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival. In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of (177)Lu-J591 (15 patients at 65 mCi/m(2), 17 at 70 mCi/m(2)) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m(2) to verify response rate and examine biomarkers. Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received (177)Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m(2)) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond. A single dose of (177)Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising. ©2013 AACR.

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Author and article information

Contributors

William Chi-shing Cho: Role: Academic Editor

Anthony Lemarié: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 28 December 2015

Publication date Collection: January 2016

Volume: 17

Issue: 1

Electronic Location Identifier: 33

Affiliations

[1 ]Laboratory of Optical Theranostics, Lobachevsky Nizhny Novgorod State University, Gagarin Ave. 23, Nizhny Novgorod 603950, Russia; nat-lekanova@ 123456yandex.ru (N.Y.S.); v.vodeneev@ 123456mail.ru (V.A.V.); andrei.zvyagin@ 123456mq.edu.au (A.V.Z.)

[2 ]Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya St, 3, Pushchino, Moscow 142290, Russia

[3 ]Prokhorov Institute of General Physics, Russian Academy of Sciences, Vavilova St, 38, Moscow 119991, Russia

[4 ]ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, Sydney 2109, Australia

Author notes

[* ]Correspondance: S_makariy@ 123456rambler.ru ; Tel.: +7-4967-739-497

Article

Publisher ID: ijms-17-00033

DOI: 10.3390/ijms17010033

PMC ID: 4730279

PubMed ID: 26729091

SO-VID: 96440d23-3c8a-44f5-83bb-3f158d0c32f1

License:

This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

Targeted Radionuclide Therapy of Human Tumors

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Abstract

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Higher order chromatin architecture

Most cited references 90

Radiotherapy and immunogenic cell death.

Cloning and characterization of the thyroid iodide transporter.

Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer.

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