A comparative study of 131I and 177Lu labeled somatostatin analogues for therapy of neuroendocrine tumours

Araújo, Elaine Bortoleti de; Filho, J.S. Caldeira; Nagamati, Lúcio Takeshi; Muramoto, Emiko; Colturato, Maria Tereza; Couto, Renata Martinussi; Pujatti, P.B.; Mengatti, Jair; Silva, C.P.G.

doi:10.1016/j.apradiso.2008.09.009

Cited by 17 publications

(9 citation statements)

References 18 publications

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“…Results demonstrated an uptake in SSTRpositive tumors 23 times higher than in SSTR-negative tumors. The results of the biodistribution were in line with the results of previous studies [34][35][36][37]. Autoradiography (Fig.…”

supporting

confidence: 91%

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts

Lindström

Spiegelberg

Raval

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose 177 Lu-DOTATATE targeting the somatostatin receptor (SSTR) is utilized for treatment of neuroendocrine tumors (NETs). Onalespib, a heat shock protein 90 (HSP90) inhibitor, has demonstrated radiosensitizing properties and may thus enhance the effect of 177 Lu-DOTATATE. Consequently, the aim of this study was to assess the potential of Onalespib in combination with 177 Lu-DOTATATE in vivo and to examine the toxicity profiles of the treatments. Methods 177 Lu-DOTATATE selectivity and distribution in NET xenografts were studied using biodistribution and autoradiography. Therapeutic effects of Onalespib in combination with 177 Lu-DOTATATE were studied in NET xenografts. Histological analyses were used to assess molecular effects from treatment and to establish toxicity profiles. Results Biodistribution and autoradiography confirmed the SSTR-selective tumor uptake of 177 Lu-DOTATATE, which was unaffected by Onalespib treatment. Immunohistochemistry verified molecular responses to Onalespib therapy in the tumors. While Onalespib and 177 Lu-DOTATATE monotherapies resulted in a 10% and 33% delay in tumor doubling time compared with control, the combination treatment resulted in a 73% delayed tumor doubling time. Moreover, combination treatment increased complete remissions threefold from 177 Lu-DOTATATE monotherapy, resulting in 29% complete remissions. In addition, histological analyses demonstrated radiation-induced glomerular injury in the 177 Lu-DOTATATE monotherapy group. The damage was decreased tenfold in the combination group, potentially due to Onalespib-induced HSP70 upregulation in the kidneys. Conclusion Treatment with Onalespib potentiated 177 Lu-DOTATATE therapy of NET xenografts with a favorable toxicity profile. Utilizing Onalespib's radiosensitizing properties with 177 Lu-DOTATATE may lead to better therapeutic results in the future and may reduce unwanted side effects in dose-limiting organs.

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supporting

confidence: 91%

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts

Lindström

Spiegelberg

Raval

et al. 2020

Eur J Nucl Med Mol Imaging

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“…Schmitt et al (0.7 mg, H69 tumor) also observed lower uptake values with a faster clearance compared to the present study (0.6 mg), with the exception for liver and blood [14]. However, de Araujo et al (1 mg, AR42J tumor) found much higher uptake values compared to the present study with 2-3 times higher values in blood, liver, pancreas, and spleen 24 h after injection [15]. only the kidneys showed a lower uptake value than the present study with a 40% reduction.…”

Section: Discussioncontrasting

confidence: 66%

“…other studies have investigated the biodistribution of 177 lu-octreotate with various results (Supplementary Table i, available online at http:// informahealthcare.com/doi/abs/10.3109/0284186X. 2015.1027001) [10,14,15,25]. Those studies were performed on BAlB/c nude mice transplanted with neuroendocrine tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

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The amount of injected ¹⁷⁷Lu-octreotate strongly influences biodistribution and dosimetry in C57BL/6N mice

2015

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The activity concentration in all tissues investigated was strongly influenced by the amount of (177)Lu-octreotate injected. Large differences in mean absorbed dose per unit injected activity were found between low (0.1-1 MBq, 0.0039-0.039 μg) and moderate amounts (5-45 MBq, 0.2-1.8 μg). Furthermore, the results clearly showed the need for better ways to estimate absorbed dose to bone marrow other than methods based on a single blood sample analysis. Since the absorbed dose to critical organs will limit the amount of (177)Lu-octreotate administered, these findings must be taken into consideration when optimizing this type of therapy.

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“…The reason is the very high SSTR expression in these cell lines and low SSTR expression in GOT2 (39). Also the activity concentrations in CA20948 in rats and AR42J in nude mice were higher than in GOT2 (43).…”

Section: Discussionmentioning

confidence: 89%

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

et al. 2011

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Abstract.To be able to evaluate new radiopharmaceuticals and optimize diagnostic and therapeutic procedures, relevant animal models are required. The aim of this study was to evaluate the medullary thyroid carcinoma GOT2 animal model by analyzing the biodistribution of 177 Lu-octreotate and 111 In-minigastrin (MG0). BALB/c nude mice, subcutaneously transplanted with GOT2, were intravenously injected with either 177 Lu-octreotate or 111 In-MG0, with or without excess of unlabeled human minigastrin simultaneously with 111 In-MG0. Animals were sacrificed 1-7 days after injection in the 177 Lu-octreotate study and 1 h after injection of 111 In-MG0. The activity concentrations in organs and tissues were determined and mean absorbed doses from 177 Lu were calculated. There was a specific tumor uptake of either 177 Lu-octreotate or 111 In-MG0. 177 Lu-octreotate samples showed high activity concentrations in tissues expressing somatostatin receptors (SSTR). For both radiopharmaceuticals the highest activity concentrations were found in the kidneys. Compared to results from similar studies in mice with another MTC cell line (TT) the biodistribution was favorable (higher tumor uptake) for the GOT2 model, while compared to other animal models expressing SSTR, the tumor uptake of 177 Lu-octreotate was modest. In conclusion, the GOT2 animal model is a valuable model for evaluation and optimization of diagnostic and therapeutic procedures using radiolabeled somatostatin, CCK2 and gastrin analogues prior to clinical studies.

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A comparative study of 131I and 177Lu labeled somatostatin analogues for therapy of neuroendocrine tumours

Cited by 17 publications

References 18 publications

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts

The amount of injected ¹⁷⁷Lu-octreotate strongly influences biodistribution and dosimetry in C57BL/6N mice

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

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A comparative study of 131I and 177Lu labeled somatostatin analogues for therapy of neuroendocrine tumours

Cited by 17 publications

References 18 publications

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts

The amount of injected 177Lu-octreotate strongly influences biodistribution and dosimetry in C57BL/6N mice

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

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The amount of injected ¹⁷⁷Lu-octreotate strongly influences biodistribution and dosimetry in C57BL/6N mice