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Octreotide Nanoparticles Showed Affinity for In Vivo MIA Paca-2 Inducted Pancreas Ductal Adenocarcinoma Mimicking Pancreatic Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma)

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Abstract

Purpose

Pancreatic Polypeptide-secreting tumor of the distal pancreas (PPoma) is a rare, difficult and indolent type of cancer with a survival rate of 5-year in only 10% of all cases. The PPoma is classified as a neuroendocrine tumor (NET) not functioning that overexpresses SSTR 2 (somatostatin receptor subtype 2). Thus, in order to improve the diagnosis of this type of tumor, we developed nanoparticulate drug carriers based on poly-lactic acid (PLA) polymer loaded with octreotide and radiolabeled with Technetium-99 m (99mTc).

Methods

PLA/PVA octreotide nanoparticles were developed by double-emulsion technique. These nanoparticles were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and radiolabeled with 99mTc by the direct via forming 99mTc-PLA/PVA octreotide nanoparticles. The safety of these nanosystems was evaluated by the MTT cell toxicity assay and their in vivo biodistribution was evaluated in xenografted inducted animals.

Results

The results showed that a 189 nm sized nanoparticle were formed with a PDI of 0,097, corroborating the monodispersive behavior. These nanoparticles were successfully radiolabeled with 99mTc showing uptake by the inducted tumor. The MTT assay corroborated the safety of the nanosystem for the cells.

Conclusion

The results support the use of this nanosystem (99mTc-PLA/PVA octreotide nanoparticles) as imaging agent for PPoma.

Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma) Radiolabeled Nanoparticles for Imaging

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Abbreviations

AFM:

Atomic Force Microscopy

CO2 :

Carbon Dioxide

DLS:

Dynamic Light Scattering

DMEM:

Dulbecco ModifiedEagle’sMinimalEssentialMedium

EDTA:

Ethylenediaminetetraaceticacid

EE:

Entrapment Efficiency

EPR:

Enhanced Permeability and Retention

FBS:

Fetal BovineSerum

HEPES:

N-2 Hydroxyethyl Piperazine-N′-2 Sulfonic Acid Ethane

ID/organ:

Dose per Organ

IPEN/CNEN:

Instituto de Pesquisas Energéticas e Nucleares/Comissão Nacional de Energia Nuclear_Institute of Energy and Nuclear Research/National Nuclear Energy Commission

μCi :

Microcurie

MBq:

Megabecquerel

MIA PACA-2:

Cells from human pancreas carcinoma

MPS:

Mononuclear Phagocytic System

MTT:

3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide

NaHCO3 :

Sodium Bicarbonate

NET:

Neuroendocrine Tumor

PDI:

Polydispersity Index

PLA:

Polylactic Acid

PP:

Pancreatic Polypeptide

PPoma:

Pancreatic Polypeptide-secreting tumor of the distal pancreas

PVA:

Poly(Vinyl Alcohol)

RPMI:

Roswell Park Memorial Institute

SC:

Subcutaneous

SD:

Standard Deviation

SnCl2 :

Stannous Chloride

SSTR 2:

Somatostatin Receptor Subtype 2

99mTc:

Technetium 99 metastable

UT:

Untreated cells

W/O:

Water/organic emulsion

W/O/W:

Water/organic solvent/water emulsion

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Authors and Affiliations

  1. Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Rio de Janeiro, Brazil

    Thaís Ligiéro Braga, Suyene Rocha Pinto, Sara Rhaissa Rezende dos Reis, Filipe Leal Portilho, Aline Oliveira da Silva de Barros, Luciana Magalhães Rebelo Alencar & Ralph Santos-Oliveira

  2. Centro de Radiofarmácia, Instituto de Pesquisas Energéticas e Nucleares, São Paulo, Brazil

    Emerson Soares Bernardes & Sofia Nascimento dos Santos

  3. Department of Physics, Federal University of Maranhão, São Luís, Maranhão, Brazil

    Luciana Magalhães Rebelo Alencar

  4. Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Eduardo Ricci-Junior

  5. Laboratory of Radiopharmacy and Nano-radiopharmaceuticals, Zona Oeste State University, Rio de Janeiro, Brazil

    Ralph Santos-Oliveira

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  1. Thaís Ligiéro Braga
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  2. Suyene Rocha Pinto
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Braga, T.L., Pinto, S.R., dos Reis, S.R.R. et al. Octreotide Nanoparticles Showed Affinity for In Vivo MIA Paca-2 Inducted Pancreas Ductal Adenocarcinoma Mimicking Pancreatic Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma). Pharm Res 36, 143 (2019). https://doi.org/10.1007/s11095-019-2678-4

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