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Year : 2013  |  Volume : 12  |  Issue : 1  |  Page : 24-26

Development of Nanoradiopharmaceuticals by Labeling Polymer Nanoparticles with Tc-99m

Laboratory of Nanoradiopharmaceuticals, Nuclear Engineering Institute, Rio de Janeiro, RJ, Brazil

Date of Web Publication25-Jun-2013

Correspondence Address:
R Santos-Oliveira
Nuclear Engineering Institute, Rua Helio de Almeida, 75, Ilha do Fundao-RJ-21941.906
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DOI: 10.4103/1450-1147.113946

PMID: 23961252

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Nanomedicine is considered as the future of modern medicine. Hence, serious global efforts are being made for the development of nanopharmaceuticals. Among all the nanopharmaceuticals developed so far, radiopharmaceuticals constitute only a very small portion, as noted in the published literature. The procedures for development of nanoradiopharmaceuticals are complex. In this paper we discuss the results of a research directed at developing nanoradiopharmaceuticals based on three different types of nanopharmaceuticals as alternative drug delivery systems.

Keywords: Drug delivery system, nanobiotechnology, nanomedicine, radiopharmaceuticals

How to cite this article:
de Carvalho Patricio B F, Albernaz M d, Santos-Oliveira R. Development of Nanoradiopharmaceuticals by Labeling Polymer Nanoparticles with Tc-99m. World J Nucl Med 2013;12:24-6

How to cite this URL:
de Carvalho Patricio B F, Albernaz M d, Santos-Oliveira R. Development of Nanoradiopharmaceuticals by Labeling Polymer Nanoparticles with Tc-99m. World J Nucl Med [serial online] 2013 [cited 2020 Apr 2];12:24-6. Available from: http://www.wjnm.org/text.asp?2013/12/1/24/113946

   Introduction Top

Polymeric microparticles used as drug delivery systems represent a field of significant potential in the field of pharmacy. Overall investment and research activities in this field have been steadily increasing in recent years. The polymeric microparticles have great stability, industrial capacity, and allow for adjustments to achieve the suitable release profile and/or direction for a particular site of action. The use of poly (lactic-co-glycolic) acid nanoparticles (PLGA NPs) has emerged as a powerful potential methodology for carrying small and large molecules of therapeutic importance, as well as scaffolds for tissue engineering applications. Polymeric micelles are used as pharmaceutical carriers to increase solubility and bioavailability of poorly water-soluble drugs. Different ligands have been used to prepare targeted polymeric micelles. [1] Liposomes have a decade-long clinical presence as nanoscale delivery systems. However, their use as delivery systems of nanoparticles is still in the preclinical development stages. Liposome-nanoparticle hybrid constructs present great opportunities in terms of nanoscale delivery system engineering for combinatory therapeutic-imaging modalities. Moreover, many novel materials are being developed in nanotechnology laboratories that often require methodologies to enhance their compatibility with the biological milieu in vitro and in vivo.

Liposomes are structurally suitable to make nanoparticles biocompatible and offer a clinically proven, versatile platform for further enhancement of pharmacological efficacy. Small iron oxide nanoparticles, quantum dots, liposomes, silica and polystyrene nanoparticles have been incorporated into liposomes for a variety of different applications. [2] Many methods of labeling liposomes and micelles with both diagnostic and therapeutic radionuclides have been developed since the initial discovery of liposomes about 40 years ago. However, their successful labeling is still in pre-clinical phase. Diagnostic radiolabels can be used to track nanometer-sized liposomes in the body in a quantitative fashion. The same goes for any nanoscale pharmaceutical, such as micelles and microparticles. [3]

The recent developments of nuclear medicine in oncology have involved numerous investigations of novel specific tumor-targeting radiopharmaceuticals as a major area of interest for both cancer imaging and therapy. The current progress in pharmaceutical nanotechnology field has been explored in the design of tumor-targeting nanoscale and microscale carriers that are able to deliver radionuclides in a selective manner to improve the outcome of cancer diagnosis and treatment. These carriers include mostly liposomes, microparticles, nanoparticles, micelles, dendrimers and hydrogels, among others. Furthermore, combining the more recent nuclear imaging multimodalities which provide high sensitivity and anatomical resolution such as PET/CT (positron emission tomography/computed tomography) and SPECT/CT (combined single photon emission computed tomography/computed tomography system) with the use of these specific tumor-targeting carriers is highly promising and will, hopefully in the near future, allow for earlier tumor detection, better treatment planning and more effective therapy. In this article we highlight the use, limitations, advantages, and possible improvements of different nano and microcarriers as potential vehicles for radionuclide delivery in cancer nuclear imaging and radiotherapy. [4]

   Materials and Methods Top


Four samples of nanoparticules were analyzed, as follows: Samples I and II micelles made up of distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG), Tetraglycerol pentastearate (TGPS), and tamoxifen; Sample III nanocapsule of PLA and tamoxifen and Sample IV also a nanocapsule made of poly lactic acid-poly ethylene glycol (PLA-PEG) and tamoxifen. All the samples were donated by the Laboratório de Tecnologia Farmacêutica USP-Ribeirão Preto.


The labeling process was done using 150 μL of (each nanoparticle under study, miceles and nanocapsule, respectively) solution incubated with stannous chloride (SnCl 2 ) solutions (80 μL/mL) (Sigma-Aldrich) for 20 minutes at room temperature. Then this solution was incubated with 100 μCi (approximately 300 μL) of technetium-99m (IPEN/CNEN) for another 10 minutes in order to label their structures with Tc-99m. In order to characterize the labeled nanoparticles, thin layer chromatography (TLC) was made using Whatman paper No. 1. The TLC was performed using 2 μL of each labeled sample in acetone (Proquimios) as the mobile phase. The radioactivity of the strips was verified in a gamma counter (Packard, Cobra II) as described in [Table 1] and [Table 2].
Table 1: Ascending chromatograms of the 99mTc-Sample I and 99mTc-Sample II compared to free pertechnetate (Na 99mTcO4-)

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Table 2: Ascending chromatography of the 99mTc-Sample III and 99mTc-Sample IV compared to Na 99mTcO4-

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Biodistribution studies were done with eight mice, two for each nanoparticle-labeled sample (I, II, III, and IV). The Institutional Review Board and the Animal Ethics Committee approved the study protocol. The labeled samples (3.7 MBq/0.2 mL) were administered after catheterization of the jugular vein. Planar images were obtained 30 minutes post-injection with a Milennium Gamma Camera (GE Healthcare, Cleveland, USA). Counts were acquired for 5 minutes in a 15% window centred at 140 KeV. Then, the animals were sacrificed and their organs removed, weighed, and the radioactivity uptake counted in a gamma counter (Packard-Cobra II). Results were expressed as percentage of injected dose per gram of tissue [Table 3].
Table 3: Biodistribution %gram per tissue versus organ of the labeled samples in mice

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   Results Top

Whatman No. 1 chromatography results are shown in [Table 1] and [Table 2]. All the nanoparticles were successfully labeled (>80%). The use of acetone as mobile phase provided an efficient separation from free Tc-99m and the labeled nanoparticle. In this case the chromatography system can be used as a well-established system for other nanoparticles following the features of the nanoparticles used in this study.

The results of bio-distribution for each labeled sample are given in [Figure 1]. Samples I, III, and IV showed liver as the main organ. Sample II showed radiopharmaceutical in the blood pool. It is important to note that none of the nanoparticles crossed the hematoencephalic barrier. Also, Samples I, III, and IV followed the hepatic system which means that their clearance is faster than the Sample III that stayed in the blood pool.
Figure 1: Biodistribution of radiolabeled samples I, II, III, and IV in mice. It may be noted that majority of the radioactivity is seen in the liver in samples I, III, and IV, while Sample II showed predominant retention in the blood pool

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   Discussion Top

The results outlined in [Table 3] appear very impressive. Sample I has one of the highest values of counts in the kidneys followed by Sample IV, which means that both of them have faster clearance. These nanoparticles also have a higher percentage uptake in the liver, corroborating the hypothesis that their clearance is a result of their fast metabolism. Sample III has a higher value in liver, but a low value in kidney. It could be due to reabsorption before the clearance of the nanoparticle. If it were true then Sample III has to be monitored closely for toxicological aspects, given that the nanoparticle is made of tamoxifen. Nevertheless, Sample II demonstrated the strangest behavior. The percentage in the liver is the lowest one which means that the nanoparticle is metabolized slowly. This information is corroborated by the percentage found in both kidneys, also the lowest when compared with all the others. The fact that Sample III accumulated in the blood pool can bring about unknown consequences related to the metabolism of this nanoparticle. Moreover, further studies must be done in order to evaluate precisely what are the mechanisms involved in this abnormal accumulation of Sample III in the blood pool.

   Conclusion Top

All nanoparticles were successfully labelled with Tc-99m. The consequences are huge since almost 90% of all radiopharmaceuticals are obtained by way of a labelling process. The results, by and large, support the use of this technique to develop nanoradiopharmaceuticals, especially those nanoradiopharmaceuticals based on Tc-99m.

   Acknowledgments Top

This study received financial support from CNPq, FAPERJ and the Universidade de São Paulo - Unidade Ribeirão Preto.

   References Top

1.Wang T, Petrenko VA, Torchilin VP. Paclitaxel-loaded polymeric micelles modified with mcf-37 cell specific phage protein: Enhanced binding to target cancer cells and increased cytotoxicity. Mol Pharm 2010;7:1007-14.  Back to cited text no. 1
2.Al-Jamal W, Al-Jamal K, Bomans P, Frederik P, Kostarelos K. Functionalized-quantum-dot-liposome hybrids as multimodal nanoparticles for cancer. Small 2008;4:1406-15.  Back to cited text no. 2
3.Phillips WT, Goins BA, Bao A. Radioactive liposomes. Rev Nanomed Nanobiotechnol 2009;1:69-83.  Back to cited text no. 3
4.Hamoudeh M, Kamleh MA, Diab R, Fessi H. Radionuclide delivery systems for nuclear imaging and radiotherapy of cancer. Adv Drug Deliv Rev 2008;60:1329-46.  Back to cited text no. 4


  [Figure 1]

  [Table 1], [Table 2], [Table 3]

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