Development and biodistrubition modeling of 99mTc-DTPA

Mohammed Bricha, El-Mehdi Hamzaoui, Kaddour Ben-Hamou, Youssef Aboussaleh, Abdelhalim Mesfioui, Abdellah Ettabia, Hassan Moulahid, Brahim Zoubir, Ahmed El-Yahyaoui

Abstract


Purpose: In this study, the team modeled the biodistribution and the efficiency of two 99m-technetium diethylene triamine penta acetate (99mTc-DTPA) based radiopharmaceuticals.

Methods: The first radiopharmaceutical (DTPA-CNESTEN) is developed at the laboratories of the radiopharmaceutical production unit of the National Center for Nuclear Energy, Sciences and Technologies (CNESTEN-Morocco), and the second one is the commercial DTPA (DTPA-ref). Freeze-dried kits were successfully radiolabeled (radiochemical purity >95%) with the 99m Tc. Then drugs were injected to male BALB/c mice. In each 2 min, 5 min, 15 min, 1 h and 2 h time points after injections we evaluate tissue’s distributions characteristics. At the end, an automatic modeling of the data were recorded from thyroid, blood and urinary excretion kinetics and biodistribution in mice using both DTPA kits. The study aimed to extract the parameters of the function used to fit the recorded data.

Results and Conclusion: the team concluded that the biodistribution of 99mTc-DTPA can be modeled using a combination of two exponential parts. Moreover, the resultant plots showed that there is strong correlation between the formula found in literature and the one derived on the basis of the fit of data sets in this study. In addition, it was found that the biodistribution behaviors of the developed kit and the commercial one were very close. The obtained results suggest that the developed DTPA has practically the same kinetics as the commercial one.


Keywords


99m-Technitium; Biodistribution; Data Fitting; DTPA; Modeling; Urinary Excretion Kinetics; CNESTEN

Full Text:

PDF

References


Jongen Y. High beam intensities for cyclotron-based radioisotope production. International Atomic Energy Agency, Technical Document 1999;1065:133-8.

Saha GB. Fundamentals of Nuclear Pharmacy. 4th ed, Springer, 1997.

Orsini F, Lorenzoni A, Erba PA, Masiani G. Radiopharmaceuticls for single-photoemission imaging and for therapy. Nuclear Oncology 2013: 21-34.

Robben J, Claude Reubi J, Pollak Y, Voorhout G. Biodistribution of [111In-DTPA-D-Phe1]- octreotide in dogs: uptake in the stomach and intestines but not in the spleen points towards interspecies differences. Nucl Med Biol. 2003;30:225-32.

Bakker WH, Albert R, Bruns C, et al. [111In- DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation. Life Sci. 1991;49:1583-91.

Bakker WH, Krenning EP, Reubi JC, et al. In vivo application of [111In-DTPA-D-Phe1]-octreotide for detection of somatostatin receptor-positive tumors in rats. Life Sci. 1991;49:1593-601.

Krenning EP, Bakker WH, Kooij PP, et al. Somatostatin receptor scintigraphy with indium-111- DTPA-D-Phe-1- octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr- 3-octreotide. J Nucl Med. 1992;33:652-8.

Yang W, Zhao Z, Fang W, Zhang X. The preparation of 99mTc-DTPA-LSA and its instant lyophilized kit for hepatic receptor imaging. Appl Radiat Isot. 2013;74:1-5.

Lee SY, Hong YD, Kim HS, Choi SJ. Synthesis and application of a novel cysteine-based DTPA-NCS for targeted radioimmunotherapy. Nucl Med Biol. 2013;40:424-9.

Volkert WA, Hoffman TJ. Therapeutic radiopharmaceuticals. Chem Rev. 1999;99:2269-92.

Boswell CA, Brechbiel MW. Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view. Nucl Med Biol. 2007;34:757-78.

Anderson CJ, Welch MJ. Radiometal-labeled agents (non-technetium) for diagnostic imaging. Chem Rev. 1999;99:2219-34.

Husin H, leong YK, Liu JS. Surface force arising from adsorbed diethylenetriaminepentacetic acid (DTPA) and related compounds and their metal ions complexes in alumina suspensions. Colloids and Surfaces A: Physicochemical and Engineering Aspects 2013;422:172-80.

Borré MC, Tesán FC, Leonardi NM, et al. Vali ation of an alternative radiochemical purity method for [99mTc] pentetate ([99mTc]DTPA). Appl Radiat Isot. 2013;82:322-4.

European Pharmacopoeia, 6th ed. Strasbourg, EDQM, 2008.

Tehnitium-99m Radiopharmaceuticals: Manufacture of kits. International Atomic Energy Agency, Technical Reports, STI/DOC/010/466, 2008.

Vallabhajosula S, Killeen RP, Osborne JR. Altered biodistribution of radiopharmaceuticals: role of radiochemical/pharmaceutical purity, physiological, and pharmacologic factors. Semin Nucl Med. 2010; 40:220-41.

World Health Organization. The WHO expert committee of specifications of pharmaceuticals preparations. Technical Report, 2008.

Maioli C, Bestetti A, Milani F, et al. Evaluation of different counting methods for use in radiochemical purity testing procedures for 99mTc-labelled radiopharmaceuticals. Appl Radiat Isot. 2008; 66:556-9.

Pinto SR, Sarcinelle MA, de Souza Albernaz M, et al. In vivo studies: comparing the administration via and the impact on the biodistribution of radiopharmaceuticals. Nucl Med Biol. 2014;41:772-4.

Saha GB, Boyd CM. A two-compartmental model analysis of plasma clearance and urinary excretion data of 111In-DTPA in dogs. Int J Nucl Med Biol. 1982;9:122-5.

Saha GB, Boyd CM. Pharmacokinetic analysis of 99mTc-radiopharmaceutical data in humans by two-compartmental model. Int J Nucl Med Biol. 1982;9:126-8.

Mathworks Inc. The Open Curve Fitting Toolbox Software: User’s Guide. 2013.

www.mathworks.com




DOI: http://dx.doi.org/10.14319/ijcto.33.18


Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

------------------------------------------------------------

International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)

© International Journal of Cancer Therapy and Oncology (IJCTO)

To make sure that you can receive messages from us, please add the 'ijcto.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.

------------------------------------------------------------

Number of visits since October, 2013
AmazingCounters.com