68Ga-DOTATOC and FDG PET Imaging of Preclinical Neuroblastoma Models

Provost, Claire; Prignon, Aurélie; Cazes, Alex; Combaret, Valérie; Delattre, Olivier; Janoueix‐Lerosey, Isabelle; Montravers, F.; Talbot, Jean-Noël

doi:10.21873/anticanres.10990

Cited by 10 publications

(8 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous study demonstrated frequent expression of SSTR subtypes in NB xenograft models: SH-SY5Y, SK-N-DZ, SK-N-AS, IMR-32 and KELLY, which is in line with our results [17]. High expression of SSTR2 has also been reported in other NB xenograft models [22,49]. A case-study of 54 NB patients reported SSTR2 expression in 44 patients, with 19 of 27 HR-NB patients expressing SSTR2 [18], confirming similar Fig.…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies demonstrate the expression of SSTRs in NBs, most prominently SSTR1 and SSTR2 [ 17 – 21 ]. Prominent proliferation and MIBG-avidity in NBs are factors that seems to correlate with high SSTR2 expression [ 19 , 22 ]. Octreotate is an SS analogue, with highest affinity towards SSTR2 and somewhat lower to SSTR4 and SSTR5 [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroblastoma xenograft models demonstrate the therapeutic potential of 177Lu-octreotate

et al. 2021

View full text Add to dashboard Cite

Background Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants. NB is a neuroendocrine tumor type with various characteristics and features, and with diverse outcome. The most malignant NBs have a 5-year survival rate of only 40–50%, indicating the need for novel and improved treatment options. 177Lu-octreotate is routinely administered for treatment of neuroendocrine tumors overexpressing somatostatin receptors (SSTR). The aim of this study was to examine the biodistribution of 177Lu-octreotate in mice bearing aggressive human NB cell lines, in order to evaluate the potential usefulness of 177Lu-octreotate for treatment of NB. Methods BALB/c nude mice bearing CLB-BAR, CLB-GE or IMR-32 tumor xenografts (n = 5–7/group) were i.v. injected with 0.15 MBq, 1.5 MBq or 15 MBq 177Lu-octreotate and sacrificed 1 h, 24 h, 48 h and 168 h after administration. The radioactivity concentration was determined for collected tissue samples, tumor-to-normal-tissue activity concentration ratios (T/N) and mean absorbed dose for each tissue were calculated. Immunohistochemical (IHC) staining for SSTR1–5, and Ki67 were carried out for tumor xenografts from the three cell lines. Results High 177Lu concentration levels and T/N values were observed in all NB tumors, with the highest for CLB-GE tumor xenografts (72%IA/g 24 h p.i.; 1.5 MBq 177Lu-octreotate). The mean absorbed dose to the tumor was 6.8 Gy, 54 Gy and 29 Gy for CLB-BAR, CLB-GE and IMR-32, respectively, p.i. of 15 MBq 177Lu-octreotate. Receptor saturation was clearly observed in CLB-BAR, resulting in higher concentration levels in the tumor when lower activity levels where administered. IHC staining demonstrated highest expression of SSTR2 in CLB-GE, followed by CLB-BAR and IMR-32. Conclusion T/N values for all three human NB tumor xenograft types investigated were high relative to previously investigated neuroendocrine tumor types. The results indicate a clear potential of 177Lu-octreotate as a therapeutic alternative for metastatic NB.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Neuroblastoma xenograft models demonstrate the therapeutic potential of 177Lu-octreotate

et al. 2021

View full text Add to dashboard Cite

show abstract

“…As recently as late 2016, 68 Ga DOT-ATATE received U.S. Food and Drug Administration approval and is now commercially available for detection of somatostatin receptorpositive neuroendocrine tumors. The advantage of this agent over 111 In pentetreotide is twofold: not only do the images show higher resolution with clearer definition than those with 111 In pentetreotide or 123 I MIBG, but the imaging protocol allows injection and imaging during the same single-day visit (53)(54)(55)(56)(57).…”

Section: Nuclear Medicinementioning

confidence: 99%

Updates in Diagnosis, Management, and Treatment of Neuroblastoma

et al. 2018

View full text Add to dashboard Cite

Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system. It is the most common extracranial solid tumor of childhood and accounts for up to 15% of all pediatric cancer fatalities. The manifestation of neuroblastoma is variable depending on the location of the tumor and on the presence or absence of paraneoplastic syndromes. The prognosis of neuroblastoma is also highly variable, ranging from spontaneous regression to widespread metastatic disease that is unresponsive to treatment. The age of the patient, stage of disease, histopathologic results, and multiple biologic factors contribute to the presurgical and pretreatment risk stratification of a patient with neuroblastoma. Multimodality anatomic imaging with ultrasonography, computed tomography, and magnetic resonance imaging, as well as functional or metabolic nuclear imaging, are essential to determining the risk status of a patient with neuroblastoma. Patients at low risk of metastasis or death receive minimal intervention and those at high risk receive multimodality treatment. New immunotherapeutic techniques and nuclear medicine-targeted therapies have emerged and are demonstrating promising response rates for patients at high risk. This article reviews updates in the diagnosis, management, and treatment of neuroblastoma that have evolved over the past 2 decades, including emphasis on presurgical risk stratification, genetic evaluation of tumors, and the use of modern, high-quality, advanced imaging modalities. RSNA, 2018.

show abstract

“…Quantifying VEGFR expression by noninvasive molecular imaging can be useful in the selection of cancer patients potentially benefiting from antiangiogenic therapy and would allow monitoring of therapeutic responses in real-time in a noninvasive way. Several preclinical and clinical approaches have been studied for imaging tumor angiogenesis, but to date, unfortunately none has emerged as a gold standard for monitoring antiangiogenic therapy or made it to approval for clinical use. , PET imaging with radiolabeled VEGFR2-targeting vascin provided good tumor SUV and T/M SUVR values compared to several other tumor-targeting peptidic tracers − and VEGF-pathway targeting recombinant protein tracers. − This could be due to the persisting accumulation in the tumor site over the 3 h scanning period. Despite a relatively high urinary excretion, the SUV in kidney (around 4.5 at 180 min) and liver (around 3 at 180 min) are higher than tumor uptake (around 0.6 at 180 min).…”

Section: Discussionmentioning

confidence: 99%

Synthetic Pept-Ins as a Generic Amyloid-Like Aggregation-Based Platform for In Vivo PET Imaging of Intracellular Targets

et al. 2021

View full text Add to dashboard Cite

Amyloid-like aggregation of proteins is induced by short amyloidogenic sequence segments within a specific protein sequence resulting in self-assembly into β-sheets. We recently validated a technology platform in which synthetic amyloid peptides (“Pept-ins”) containing a specific aggregation-prone region (APR) are used to induce specific functional knockdown of the target protein from which the APR was derived, including bacterial, viral, and mammalian cell proteins. In this work, we investigated if Pept-ins can be used as vector probes for in vivo Positron Emission Tomography (PET) imaging of intracellular targets. The radiolabeled Pept-ins [68Ga]Ga-NODAGA-PEG4-vascin (targeting VEGFR2) and [68Ga]Ga-NODAGA-PEG2-P2 (targeting E. coli) were evaluated as PET probes. The Pept-in based radiotracers were cross-validated in a murine tumor and muscle infection model, respectively, and were found to combine target specificity with favorable in vivo pharmacokinetics. When the amyloidogenicity of the interacting region of the peptide is suppressed by mutation, cellular uptake and in vivo accumulation are abolished, highlighting the importance of the specific design of synthetic Pept-ins. The ubiquity of target-specific amyloidogenic sequence segments in natural proteins, the straightforward sequence-based design of the Pept-in probes, and their spontaneous internalization by cells suggest that Pept-ins may constitute a generic platform for in vivo PET imaging of intracellular targets.

show abstract

68Ga-DOTATOC and FDG PET Imaging of Preclinical Neuroblastoma Models

Abstract: Abstract. Background

Cited by 10 publications

References 15 publications

Neuroblastoma xenograft models demonstrate the therapeutic potential of 177Lu-octreotate

Neuroblastoma xenograft models demonstrate the therapeutic potential of 177Lu-octreotate

Updates in Diagnosis, Management, and Treatment of Neuroblastoma

Synthetic Pept-Ins as a Generic Amyloid-Like Aggregation-Based Platform for In Vivo PET Imaging of Intracellular Targets

Contact Info

Product

Resources

About