Feasibility and advantage of adding 131I-MIBG to 90Y-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors

Bushnell, David; Madsen, Mark T.; O'cdorisio, Thomas; Menda, Yusuf; Muzahir, Saima; Ryan, Randi; O’Dorisio, M. Sue

doi:10.1186/s13550-014-0038-2

Cited by 17 publications

(11 citation statements)

References 35 publications

(36 reference statements)

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“…The addition of 131 I-MIBG to 90 Y DOTA-Phe1-Tyr3-octreotide ( 90 Y-DOTATOC) in patients with advanced stage midgut NETs confirmed the feasibility of this strategy. 27 Of particular interest is how these findings will translate to new PRRT agents that possess higher target affinities than traditional SSTR agonists. In a small pilot study a SST2-receptor antagonist, 177 Lu-DOTA-JR11, was shown to possess superior intratumoural residence time and higher tumour uptake over 177 Lu-DOTA-TATE; properties that make it well-suited to a radiosensitisation strategy.…”

Section: Peptide-based Trtmentioning

confidence: 99%

Targeted radionuclide therapy in combined-modality regimens

Gill

Falzone

et al. 2017

The Lancet Oncology

125

126

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Targeted radionuclide therapy (TRT) is a branch of cancer medicine concerned with the use of radioisotopes, radiolabelled molecules, nanoparticles, or microparticles that either naturally accumulate in or are designed to target tumours. TRT combines the specificity of molecular and sometimes physical targeting with the potent cytotoxicity of ionising radiation. Targeting vectors for TRT include antibodies, antibody fragments, proteins, peptides, and small molecules. The diversity of available carrier molecules, together with the large panel of suitable radioisotopes with unique physicochemical properties, allows vector-radionuclide pairings to be matched to the molecular, pathological, and physical characteristics of a tumour. Some pairings are designed for dual therapeutic and diagnostic applications. Use of TRT is increasing with the adoption into practice of radium-223 dichloride for the treatment of bone metastases and with the ongoing clinical development of, among others, Lu-dodecanetetraacetic acid tyrosine-3-octreotate (DOTATATE) for the treatment of neuroendocrine tumours andY-microspheres for the treatment of hepatic tumours. The increasing use of TRT raises the question of how best to integrate TRT into multimodality protocols. Achievements in this area and the future prospects of TRT are evaluated in this Review.

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Section: Peptide-based Trtmentioning

confidence: 99%

Targeted radionuclide therapy in combined-modality regimens

Gill

Falzone

et al. 2017

The Lancet Oncology

125

126

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“…In einer größeren retrospektiven Studie bei 98 Patienten [587] mit metastasierten NEN konnte ein medianes Überleben von 2,3 Jahren nach MIBG-Therapie erzielt werden, als häufigste Nebenwirkung wurde eine relevante Knochenmarkstoxizität bei 13 % der Patienten beschrieben. Bisher existieren keine vergleichenden Studien zwischen I-131-MIBG-Therapie und PRRT, jedoch wurde über eine höhere erzielbare Tumordosis durch eine kombinierte Behandlung mit I-131-MIBG und Y-90-DOTATOC berichtet [588]. Über Fallberichte hinausgehende Ergebnisse zur Sequenztherapie liegen jedoch nicht vor.…”

Section: Empfehlung Konsensunclassified

S2k-Leitlinie Neuroendokrine Tumore

Gastroenterologie¹,

Tumoren²,

e.V.³

et al. 2018

Z Gastroenterol

127

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“…So far, only few studies have reported the combined use of different radiopharmaceuticals for TRT [ 26 ]. Previous studies performed TRT of neuroendocrine tumors via the combined use of high-energy and long-path 90 Y-somatostatin analog with its medium energy and short path 177 Lu analog for combating tumors of various sizes [ 27 ], or with 131 I-metaiodobenzylguanidine (a norepinephrine analog) for increasing the dose delivered to the tumor site [ 28 ]. Different from their treatment concepts, the present study suggested the combination of different radiopharmaceuticals (may not be limited to the currently used agents) to improve the intratumoral radioactivity distribution and thus enhance the therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Uniform intratumoral distribution of radioactivity produced using two different radioagents, 64Cu-cyclam-RAFT-c(-RGDfK-)4 and 64Cu-ATSM, improves therapeutic efficacy in a small animal tumor model

et al. 2018

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BackgroundThe present study proposed a new concept for targeted radionuclide therapy (TRT) to improve the intratumoral distribution of radioactivity using two different radiopharmaceuticals. We examined the efficacy of a combination of a tetrameric cyclic Arg-Gly-Asp (cRGD) peptide-based radiopharmaceutical, 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD, an αVβ3 integrin [αVβ3] tracer), and 64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM, a supposed tracer for hypoxic metabolism) in a small animal tumor model.ResultsMice with subcutaneous αVβ3-positive U87MG glioblastoma xenografts were used. The intratumoral distribution of a near-infrared dye, Cy5.5-labeled RAFT-c(-RGDfK-)4 (Cy5.5-RaftRGD), 64Cu-RaftRGD, and 64Cu-ATSM was visualized by fluorescence imaging and autoradiography of the co-injected Cy5.5-RaftRGD with 64Cu-RaftRGD or 64Cu-ATSM at 3 h postinjection. Mice were treated with a single intravenous dose of the vehicle solution (control), 18.5 or 37 MBq of 64Cu-RaftRGD or 64Cu-ATSM, or a combination (18.5 MBq of each agent). The tumor volume, tumor cell proliferation, body weight, survival, and tumor and organ uptake of radiopharmaceuticals were assessed. It was shown that Cy5.5-RaftRGD colocalized with 64Cu-RaftRGD and could be used as a surrogate for the radioactive agent. The intratumoral distribution of Cy5.5-RaftRGD and 64Cu-ATSM was discordant and nearly complementary, indicating a more uniform distribution of radioactivity achievable with the combined use of 64Cu-RaftRGD and 64Cu-ATSM. Neither 64Cu-RaftRGD nor 64Cu-ATSM showed significant effects on tumor growth at 18.5 MBq. The combination of both (18.5 MBq each) showed sustained inhibitory effects against tumor growth and tumor cell proliferation and prolonged the survival of the mice, compared to that by either single agent at 37 MBq. Interestingly, the uptake of the combination by the tumor was higher than that of 64Cu-RaftRGD alone, but lower than that of 64Cu-ATSM alone. The kidneys showed the highest uptake of 64Cu-RaftRGD, whereas the liver exhibited the highest uptake of 64Cu-ATSM. No obvious adverse effects were observed in all treated mice.ConclusionsThe combination of 64Cu-RaftRGD and 64Cu-ATSM achieved an improved antitumor effect owing to the more uniform intratumoral distribution of radioactivity. Thus, combining different radiopharmaceuticals to improve the intratumoral distribution would be a promising concept for more effective and safer TRT.Electronic supplementary materialThe online version of this article (10.1186/s13550-018-0407-3) contains supplementary material, which is available to authorized users.

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Feasibility and advantage of adding 131I-MIBG to 90Y-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors

Cited by 17 publications

References 35 publications

Targeted radionuclide therapy in combined-modality regimens

Targeted radionuclide therapy in combined-modality regimens

S2k-Leitlinie Neuroendokrine Tumore

Uniform intratumoral distribution of radioactivity produced using two different radioagents, 64Cu-cyclam-RAFT-c(-RGDfK-)4 and 64Cu-ATSM, improves therapeutic efficacy in a small animal tumor model

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