REVIEW ABOUT RADIOPHARMACEUTICALS: PREPARATION, RADIOACTIVITY, AND APPLICATIONS
Keywords:Radiopharmaceuticals, Thyroid gland, Bone pain, Diagnosis, Therapeutic effect, Tumors, Myocardial and cerebral perfusion
In the recent few decades, there was a growth in the field of radioactive medicinal agents called radiopharmaceuticals. Radiopharmaceuticals are consisting of radioactive materials called radioisotopes. Radiopharmaceuticals were recently used in both therapeutic and diagnostic purposes. More than 100 radioactive substances are used in nuclear medicine. According to the decay of radioactive substances, there are three types of radioactive decays, alpha particles, beta particles, and gamma radiations. Alpha particles consist of two protons and two neutrons with large mass and charge so it has no penetration power into the skin and has a destructive effect. Beta particles have less charge and less mass so, they can penetrate the tissue and have a less destructive effect than alpha particles and can be used in therapy. Gamma radiations have no mass or charge so they can penetrate the deep tissue of organs so used in diagnosis by imaging using a gamma camera. The radiopharmaceuticals were established in the diagnostic purpose and treatment of several diseases as thyroid gland cancer, hyperthyroidism, bone pain metastasis, kidney dysfunction, and myocardial and cerebral perfusion. The radioactive substance can also be used in the sterilization of thermo-labile substances as syringes, catheters, vitamins, hormones, and surgical dressing. The field of nuclear medicine has several advantages as localization of tumors, safe diagnosis, no accumulation of radiation, and high therapeutic efficacy. Nowadays, the branch of nuclear pharmacy is directed to introduce new radioactive pharmaceutical agents which will be important and effective in the treatment of cancer. The growth in the field of radiopharmaceuticals is important to help millions of patients suffering from tumors all over the world. The data of this review were collected by searching in Google Scholar and PubMed using the following keywords.
Nadugopal B, Swain SS, Ojha SK, Meher CP. Impact of radiopharmaceuticals in the healthcare system. PharmaTutor 2017;5:23–31.
Heske SM, Hladik WB, Laven DL, Kavula MP. Status of radiologic pharmacy education in colleges of pharmacy. Am J Pharm Educ 1996;60:152–61.
Skanjeti A, Miranti A, Yabar GMD, Bianciotto D, Trevisiol E, Stasi M, et al. A simple and accurate dosimetry protocol to estimate activity for hyperthyroidism treatment. Nucl Med Rev 2015;18:13–8.
Nakagawa Y, Mori K, Hoshikawa S, Ozaki H, Ito S, Yoshida K. Development of subclinical hyperthyroidism due to Graves’ disease in a hypothyroid woman who had undergone hemithyroidectomy for adenomatous goiter and radiotherapy for nasopharyngeal cancer. Endocr J 2007;54:35–7.
Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. In: Seminars in nuclear medicine. Elsevier; 2010. p. 89–104.
Paes FM, Ernani V, Hosein P, Serafini AN. Radiopharmaceuticals: when and how to use them to treat metastatic bone pain. J Support Oncol 2011;9:197–205.
Taylor AT. Radionuclides in nephrourology, part 1: radiopharmaceuticals, quality control, and quantitative indices. J Nucl Med 2014;55:608–15.
Pauwels EK, McCready VR, Stoot JH, van Deurzen DF. The mechanism of accumulation of tumor-localizing radiopharmaceuticals. Eur J Nucl Med 1998;25:277–305.
Volkert WA, Hoffman TJ. Therapeutic radiopharmaceuticals. Chem Rev 1999;99:2269–92.
Dar M, Masoodi M, Farooq S. Medical uses of radiopharmaceuticals. PharmaTutor 2015;3:24–9.
Jalilian AR, Beiki D, Hassanzadeh Rad A, Eftekhari A, Geramifar P, Eftekhari M. Production and clinical applications of radiopharmaceuticals and medical radioisotopes in Iran. In: seminars in nuclear medicine. Elsevier; 2016. p. 340–58.
Ferro Flores G, E Ocampo Garcia B, Melendez Alafort L. Development of specific radiopharmaceuticals for infection imaging by targeting infectious micro-organisms. Curr Pharm Des 2012;18:1098–106.
Kost SD, Dewaraja YK, Abramson RG, Stabin MG. VIDA: a voxel-based dosimetry method for targeted radionuclide therapy using geant4. Cancer Biother Radiopharm 2015;30:16–26.
Del Guerra A, Panetta D. Fundamentals of natural and artificial radioactivity and interaction of ionizing radiations with the matter. In: Nuclear Medicine Textbook. Springer; 2019. p. 3–19.
Dobrescu L, Stanciu S, Pleșca C, Ropot A. Towards an integrated medical system for radiological medical imaging investigations. Res J Med Med Sci 2017;120:5.
Radvanyi P, Villain J. The discovery of radioactivity. Comptes Rendus Phys 2017;18:544–50.
Bruce Sodee D. The evaluation of metastatic thyroid carcinoma with technetium-99m pertechnetate. Radiology 1967;88:145–7.
Tjuvajev JG, Macapinlac HA, Daghighian F, Scott AM, Ginos JZ, Finn RD, et al. Imaging of brain tumor proliferative activity with iodine-131-iododeoxyuridine. J Nucl Med 1994;35:1407–17.
Gu X, Jiang M, Pan D, Cai G, Zhang R, Zhou Y, et al. Preliminary evaluation of novel 18F-AlF-NOTA-IF7 as a tumor imaging agent. J Radioanal Nucl Chem 2016;308:851–6.
Hupf HB, Eldridge JS, Beaver JE. Production of Iodine-123 for medical applications. Int J Appl Radiat Isot 1968;19:345–51.
Smith Jones PM, Stolz B, Bruns C, Albert R, Reist HW, Fridrich R, et al. Gallium-67/gallium-68-[DFO]-octreotide-a potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in vitro and preliminary in vivo studies. J Nucl Med 1994;35:317–25.
Stohl A, Seibert P, Wotawa G, Arnold D, Burkhart JF, Eckhardt S, et al. Xenon-133 and caesium-137 releases into the atmosphere from the fukushima dai-ichi nuclear power plant: determination of the source term, atmospheric dispersion, and deposition. Atmospheric Chem Phys 2012;12:2313–43.
Miyagawa M, Kumano S, Sekiya M, Watanabe K, Akutzu H, Imachi T, et al. Thallium-201 myocardial tomography with intravenous infusion of adenosine triphosphate in the diagnosis of coronary artery disease. J Am Coll Cardiol 1995;26:1196–201.
Robinson RG, Preston DF, Spicer JA, Baxter KG. Radionuclide therapy of intractable bone pain: emphasis on strontium-89. Semin Nucl Med 1992;22:28–32.
Whitmore Willet F, Hilaris Basil, Grabstald Harry. Retropubic implantation of iodine 125 in the treatment of prostatic cancer. J Urol 1972;108:918–20.
Van de Poll MC, Versluis A, Rasker JJ, Jurjens H, Woldring MG. Labelling of bleomycin with cobalt-57, indium-111, technetium-99m, mercury-197, lead-203, and copper-67. Nuklearmedizin 1976;15:86–90.
Singh A, Holmes RA, Farhangi M, Volkert WA, Williams A, Stringham LM, et al. Human pharmacokinetics of samarium-153 EDTMP in metastatic cancer. J Nucl Med 1989;30:1814–8.
Adam MJ, Wilbur DS. Radiohalogens for imaging and therapy. Chem Soc Rev 2005;34:153–63.
Willowson KP. Production of radionuclides for clinical nuclear medicine. Eur J Phys 2019;40:043001.
Blower JE, Cooper MS, Imberti C, Ma MT, Marshall C, Young JD, et al. The radiopharmaceutical chemistry of the radionuclides of gallium and indium. In: radiopharmaceutical chemistry. Springer; 2019. p. 255–71.
Eppard E, Wuttke M, Nicodemus PL, Rösch F. Ethanol-based post-processing of generator-derived 68Ga toward kit-type preparation of 68Ga-radiopharmaceuticals. J Nucl Med 2014;55:1023–8.
Reed BC. An examination of the potential fission-bomb weaponizability of nuclides other than 235U and 239Pu. Am J Phys 2017;85:38–44.
Qaim SM, Spahn I, Scholten B, Neumaier B. Uses of alpha particles, especially in nuclear reaction studies and medical radionuclide production. Radiochim Acta 2016;104:601–24.
Abdessamad Didi, Ahmed Dadouch, Hassane El Bekkouri. Feasibility study for production of Iodine-131 using dioxide of tellurium-130. Int J Pharm Pharm Sci 2016;8:e331.
Debnath S, Babu MN. Radiopharmaceuticals and their therapeutic applications in the health care system. Asian J Res Pharm Sci 2015;5:221–6.
Hung JC, Ponto JA, Gadient KR, Frie JA, Aksamit CM, Enquist CL, et al. Deficiencies of product labeling directions for the preparation of radiopharmaceuticals. J Am Pharm Assoc 2004;44:30–5.
Parigger CG, Dackman M, Hornkohl JO. Time-resolved spectroscopy measurements of hydrogen-alpha,-beta, and gamma emissions. Appl Opt 2008;47:G1–G6.
Lassmann M, Eberlein U. Targeted alpha-particle therapy: imaging, dosimetry, and radiation protection. Ann ICRP 2018;47:187–95.
Maulany GJ, Manggau FX, Jayadi J, Waremra RS, Fenanlampir CA. Radiation detection of alfa, beta, and gamma rays with geiger muller detector. Int J Mech Eng Technol 2018;9:21–7.
Magill J, Galy J. Radioactivity radionuclides radiation. Vol. 1. Springer Science and Business Media; 2004.
Blankenberg FG, Strauss HW. Nuclear medicine applications in molecular imaging. J Magn Reson Imaging Off J Int Soc Magn Reson Med 2002;16:352–61.
Hughes DK. Nuclear medicine and infection detection: the relative effectiveness of imaging with 111In-oxine-, 99mTc-HMPAO-, and 99mTc-stannous fluoride colloid-labeled leukocytes and with 67Ga-citrate. J Nucl Med Technol 2003;31:196–201.
Tryciecky EW, Gottschalk A, Ludema K. Oncologic imaging: interactions of nuclear medicine with CT and MRI using the bone scan as a model. In: Seminars in nuclear medicine. Elsevier; 1997. p. 142–51.
Vassiliou V, Andreopoulos D, Frangos S, Tselis N, Giannopoulou E, Lutz S. Bone metastases: assessment of therapeutic response through radiological and nuclear medicine imaging modalities. Clin Oncol 2011;23:632–45.
Love C, Palestro CJ. Nuclear medicine imaging of bone infections. Clin Radiol 2016;71:632–46.
Nakajima K, Matsumoto N, Kasai T, Matsuo S, Kiso K, Okuda K. Normal values and standardization of parameters in nuclear cardiology: Japanese Society of Nuclear Medicine working group database. Ann Nucl Med 2016;30:188–99.
Saha GB. Therapeutic uses of radiopharmaceuticals in nuclear medicine. In: Fundamentals of Nuclear Pharmacy. Springer; 2018. p. 373–83.
Loke KS, Padhy AK, Ng DC, Goh AS, Divgi C. Dosimetric considerations in radioimmunotherapy and systemic radionuclide therapies: a review. World J Nucl Med 2011;10:122.
Almen A, Mattsson S. Radiological protection of foetuses and breastfed children of occupationally exposed women in nuclear medicine–challenges for hospitals. Phys Med 2017;43:172–7.
Rubio IT, Diaz Botero S, Esgueva A, Rodriguez R, Cortadellas T, Cordoba O, et al. The superparamagnetic iron oxide is equivalent to the Tc99 radiotracer method for identifying the sentinel lymph node in breast cancer. Eur J Surg Oncol EJSO 2015;41:46–51.
Davenport MS, Cohan RH, Caoili EM, Ellis JH. Repeat contrast medium reactions in premedicated patients: frequency and severity. Radiology 2009;253:372–9.
Khalil M. A snapshot on nuclear cardiac imaging. Egypt J Nucl Med 2017;15:1-5.
Silberstein EB. Prevalence of adverse reactions to positron-emitting radiopharmaceuticals in nuclear medicine. J Nucl Med 1998;39:2190.
Abell TL, Camilleri M, Donohoe K, Hasler WL, Lin HC, Maurer AH, et al. Consensus recommendations for gastric emptying scintigraphy: a joint report of the American neurogastroenterology and motility society and the society of nuclear medicine. J Nucl Med Technol 2008;36:44–54.
Babu K, Jayaraaj IA, Prabhakar J. Effect of abnormal thyroid hormone changes in lipid peroxidation and antioxidant imbalance in hypothyroid and hyperthyroid patients. Int J Biol Med Res 2011;2:1122–6.
Meier DA, Brill DR, Becker DV, Clarke SE, Silberstein EB, Royal HD, et al. Procedure guideline for therapy of thyroid disease with 131Iodine. J Nucl Med 2002;43:856–61.
Düsman E, Berti AP, Mariucci RG, Lopes NB, Vicentini VEP. Mutagenicity of diagnostic and therapeutical doses of radiopharmaceutical iodine-131 in wistar rats. Radiat Environ Biophys 2011;50:579.
Bonnema SJ, Hegedüs L. Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Endocr Rev 2012;33:920–80.
Weetman AP. Radioiodine treatment for benign thyroid diseases. Clin Endocrinol (Oxf) 2007;66:757–64.
Nielsen OS, Munro AJ, Tannock IF. Bone metastases: pathophysiology and management policy. J Clin Oncol 1991; 9:509–24.
Lin A, Ray ME. Targeted and systemic radiotherapy in the treatment of bone metastasis. Cancer Metastasis Rev 2006;25:669–75.
Liberal FDG, Tavares AAS, Tavares JMR. Palliative treatment of metastatic bone pain with radiopharmaceuticals: a perspective beyond strontium-89 and Samarium-153. Appl Radiat Isot 2016;110:87–99.
Reang P, Gupta M, Kohli K. Biological response modifiers in cancer. Medscape Gen Med 2006;8:33.
Leahy MF, Seymour JF, Hicks RJ, Turner JH. Multicenter phase II clinical study of iodine-131-rituximab radioimmunotherapy in relapsed or refractory indolent non-Hodgkin’s lymphoma. J Clin Oncol 2006;24:4418–25.
Coffey RJ, Flickinger JC, Bissonette DJ, Lunsford LD. Radiosurgery for solitary brain metastases using the cobalt-60 gamma unit: methods and results in 24 patients. Int J Radiat Oncol Biol Phys 1991;20:1287–95.
Fourquet A, Campana F, Mosseri V, Cetingoz R, Luciani S, Labib A, et al. Iridium-192 versus cobalt-60 boost in 3–7 cm breast cancer treated by irradiation alone: final results of a randomized trial. Radiother Oncol 1995;34:114–20.
Nordyke RA, Gilbert FI. Optimal iodine-131 dose for eliminating hyperthyroidism in graves’ disease. J Nucl Med 1991;32:411–6.
De Klerk JMH, Van Dijk A, Van Het Schip AD, Zonnenberg BA, Van Rijk PP. Pharmacokinetics of rhenium-186 after administration of rhenium-186-HEDP to patients with bone metastases. J Nucl Med 1992;33:646–51.
Sangro B, Bilbao JI, Boan J, Martinez Cuesta A, Benito A, Rodriguez J, et al. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma. Int J Radiat Oncol 2006;66:792–800.
Serafini AN. Systemic metabolic radiotherapy with samarium-153 EDTMP for the treatment of painful bone metastasis. Q J Nucl Med Mol Imaging 2001;45:91.
Lewington VJ, McEwan AJ, Ackery DM, Bayly RJ, Keeling DH, Macleod PM, et al. A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur J Cancer Clin Oncol 1991;27:954–8.
Fettich J, Padhy A, Nair N, Morales R, Tanumihardja M, Riccabonna G, et al. Comparative clinical efficacy and safety of phosphorus-32 and strontium-89 in the palliative treatment of metastatic bone pain: results of an IAEA coordinated research project. World J Nucl Med 2003;2:226–31.
Knut L. Radiosynovectomy in the therapeutic management of arthritis. World J Nucl Med 2015;14:10.
Kraeber Bodere F, Campion L, Rousseau C, Bourdin S, Chatal JF, Resche I. Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement. Eur J Nucl Med 2000;27:1487–93.
Boschi A, Martini P, Pasquali M, Uccelli L. Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons. Drug Dev Ind Pharm 2017;43:1402–12.
Curtis C, Gamez JE, Singh U, Sadowsky CH, Villena T, Sabbagh MN, et al. Phase 3 trial of flutemetamol labeled with radioactive fluorine 18 imaging and neuritic plaque density. JAMA Neurol 2015;72:287–94.
Vente MA, de Wit TC, Van Den Bosch MA, Bult W, Seevinck PR, Zonnenberg BA, et al. Holmium-166 poly (L-lactic acid) microsphere radioembolization of the liver: technical aspects studied in a large animal model. Eur Radiol 2010;20:862–9.
Maxon III HR, Smith HS. Radioiodsne-131 in the diagnosis and treatment of metastatic weil differentiated thyroid cancer. Endocrinol Metab Clin North Am 1990;19:685–718.
Mandel SJ, Shankar LK, Benard F, Yamamoto A, Alavi A. Superiority of iodine-123 compared with iodine-131 scanning for thyroid remnants in patients with differentiated thyroid cancer. Clin Nucl Med 2001;26:6–9.
Mohammed A. El-Motaleb, Amal S Farrag, Ismail T Ibrahim, Mona O Sarhan, Magda F Ismail. Preparation and molecular modeling of radioiodopropranolol as a novel potential radiopharmaceutical for lung perfusion scan. Int J Pharm Pharm Sci 2015;7:110-6.
Visakh T, Suresh Sukumar, Abhimanyu Pradhan. Estimation of entrance surface radiation dose to thyroid region computed tomography brain examination. Asian J Pharm Clin Res 2019;12:121-3.
Falk RH, Lee VW, Rubinow A, Hood WB, Cohen AS. Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis. Am J Cardiol 1983;51:826–30.
Ebaugh FG, Emerson CP, Ross JF, Aloia R, Halperin P, Richards H. The use of radioactive chromium 51 as an erythrocyte tagging agent for the determination of red cell survival in vivo. J Clin Invest 1953;32:1260–76.
Stevens LA, Nolin TD, Richardson MM, Feldman HI, Lewis JB, Rodby R, et al. Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations. Am J Kidney Dis 2009;54:33–42.
Bekerman C, Hoffer PB, Bitran JD. The role of gallium-67 in the clinical evaluation of cancer. Semin Nucl Med 1984; 14:296–323.
Zaret BL. Myocardial imaging with radioactive potassium and its analogs. Prog Cardiovasc Dis 1977;20:81–94.
Gross GJ, Warltier DC, Hardman HF, Somani P. The effect of ouabain on nutritional circulation and regional myocardial blood flow. Am Heart J 1977;93:487–95.
Pineda JD, Lee T, Ain K, Reynolds JC, Robbins J. Iodine-131 therapy for thyroid cancer patients with elevated thyroglobulin and negative diagnostic scan. J Clin Endocrinol Metab 1995;80:1488–92.
O’Keefe SJ, Ogden JM, Young GO, Dicker J, Marks IS. Measurement of pancreatic enzyme synthesis in humans. Int J Pancreatol 1989;4:13–27.
Tang CW, Maletskos CJ. Elimination of sodium-24 and potassium-42 interferences inactivation analysis of biological samples. Science 1970;167:52–4.
Sullivan PJ, Burke WM, Burch WM, Lomas FE. A clinical comparison of Technegas and xenon-133 in 50 patients with suspected pulmonary embolus. Chest 1988;94:300–4.
Okayama K, Kurata C, Tawarahara K, Wakabayashi Y, Chida K, Sato A. Diagnostic and prognostic value of myocardial scintigraphy with thallium-201 and gallium-67 in cardiac sarcoidosis. Chest 1995;107:330–4.
Hartman AW, Nesbitt Jr RU, Smith FM, Nuessle NO. Viscosities of acacia and sodium alginate after sterilization by cobalt-60. J Pharm Sci 1975;64:802–5.