Technetium-99m Radiopharmaceuticals: A Review on Basic and Applied Aspects


  • M. Khan PINSTECH
  • Q. Mehmood PINSTECH


Technetium-99m (99mTc) usage is increasing worldwide at a rate of 32% per annum. Enriched Uranium-
235 is irradiated at nuclear reactor and subsequent process produces Molybdenum-99 (99Mo) which
decays to 99mTc, and 99mTc converts to 99gTc. Organic molecules are used as 99mTc carriers, e.g., 99mTcmercaptoactyltriglycine.
99mTc is excreted from body with feces and urine. It is estimated that 0.22%–
38.41% of 99mTc remains in needles and rest is injected to the patient. Forty generators per week are
supplied to medical centers in Pakistan and 1.72 x105 Bq/y 99gTc is returned as radioactive waste. Every
used 99Mo/99mTc generator contains 99gTc ~ 83.3 Bq. 99gTc radioactive waste is increasing world-wide, as
its global use is ~4.5×1014 Bq/week. No satisfactory method exists for 99gTc immobilization although
incorporation of 99gTc into Fe(III) or Sn(IV) oxide matrix before glass immobilization is suggested. The
present review covers all aspect of 99mTc radiopharmaceutical life-cycle and suggests options for 99gTc
radioactive waste management.

Author Biographies


Senior Scientist at PINSTECH.

Q. Mehmood, PINSTECH




G.A. Andrews, “Radioactive pharmaceuticalsâ€, New York: US Atomic Energy Commission, Report, 1966.

G.A. Andrews, R.M. Kniseley, H.N. Wagner and E.B. Anderson, ''Radioactive pharmaceuticals'', Am. J. Med. Sci., vol. 253, pp. 246, 1967.

C. Perrier and E. Segrè, "Some chemical properties of element 43", J. Chem. Phys., vol. 5, no. 24, pp. 712-716, 1937.

G. Subramanian, J.G. McAfee, E.G. Bell, R.J. Blair, and R.E. O’Mara,"99mTc-labeled polyphosphate as skeletal imaging agentâ€, Radiology, vol. 102, no. 3, 1972.

A. Vértes, S. Nagy, Z. Klencsár, R.G. Lovas and F. Rösch, “Handbook of Nuclear Chemistryâ€, Basics of Nuclear Science, Vol. 2. New York: Springer Science & Business Media, 2010.

M. Khan, W. Um, W-S. Kim, J. Heo, H. Kim, and S. Chang, ''Synthesis of rhenium-doped tin dioxide for technetium radioactive waste immobilizationâ€, J. Nucl. Mater., vol. 505, pp.134–142, 2018.

K. Risto, ''The effect of dopant’s valence (+III and +V) on the anion/cation uptake properties of antimony-doped tin dioxide", Cent. Eur. J. Chem., vol. 8, pp. 1179-1184, 2010.

R.J. Kowalsky, “Technetium radiopharmaceutical chemistry Tc complexes, New Mexicoâ€, UNM Health Sciences Center College of Pharmacy, Albuquerque, 2006.

A. Boschi, P. Martini, M. Pasquali and L. Uccelli, "Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons", Drug Dev. Ind. Pharm., vol. 43, no. 9, pp. 1402-1412, 2017.

B.A. Jansson, M.B. Göransson and B.N. Ågren, "Adsorption of some technetium-99m radiopharmaceuticals onto disposable plastic syringes", J. Nucl. Med. Technol., vol. 26, no. 3, pp. 196-199, 1998.

G. Subramanian, J.G. McAfee, E.G. Bell, R.J. Blair, and R.E. O’Mara,"99mTc-EHDP: A potential radiopharmaceutical for skeletal imaging", J. Nucl. Med., vol. 13, pp. 947-950, 1972.

F.A. Cotton and G. Wilkinson, “Advanced inorganic chemistryâ€, New York: Wiley, 1988.

L.I. Lebedeva and K. Kyong, ''Interaction between phosphorous (V), molybdenum (VI) and aluminum (III) in weak acid solutions'', Vestn Leningr Univ., vol. 23, pp. 127-131, 1968.

H.L. Atkins, “Technetium-99m radiopharmaceuticals: Manufacture of kitsâ€, Technical Reports Series No. 466, International Atomic Energy Agency, Vienna, Austria, pp. 315-367, 1975.

R.J. Kowalsky, “Radiopharmaceuticals in nuclear pharmacy and nuclear medicineâ€, Annals of Pharmacotherapy, 3rd edition, Ed.: P. Jeffery, Albuquerque, University of New Mexico, Mexico, p. 1272, 2012.

K.E. Linder, J. Gougoutas, M. Malley, A.D. Nunn and S. Unger, “A reâ€assessment of the oxidation state of Tc-(DMG)-3-(μâ€OH) SnCl3: Evidence for Tc (III)", J. Labelled Comp. Radiopharm., vol. 26, no. 1â€12, pp. 266-268, 1989.

V.J. Molinski, ''A review of 99mTc generator technology'', Appl. Radiat. Isot., no. 33, pp. 811-819, 1982.

C. Bolzati, F. Refosco, A. Marchiani and P. Ruzza, "99mTc-radiolabelled peptides for tumour imaging: present and future", Curr. Med. Chem. Current., vol. 17, no. 24, pp. 2656-2683, 2010.

F.H. Fahey, S.T. Treves and S.J. Adelstein, "Minimizing and communicating radiation risk in pediatric nuclear medicine", J. Nucl. Med., vol. 52, no. 8, pp. 1240-1251, 2011.

G. Bedetti, C. Pizzi, G. Gavaruzzi, F. Lugaresi, A. Cicognani and Eugenio Picano, "Suboptimal awareness of radiologic dose among patients undergoing cardiac stress scintigraphy", J. Am. Coll. Radiol., vol. 5, no. 2, pp. 126-131, 2008.

G. Saha, “Fundamentals of Nuclear Pharmacyâ€, 3rd ed., New York: Springer, 1992.

J.R. Ballinger, ''Pitfalls and limitations of SPECT, PET and therapeutic radiopharmaceuticals'', Semin. Nucl. Med., vol. 45, pp. 470-478, 2015.

J.L.P. Gómez and M.T.A. Gutiérrez, "Radiochemical purity testing of 99mTc-labelled radiopharmaceuticals: Nothing, except everything, is enough", Rev. Esp. Med. Nucl. Imagen. Mol., vol. 37, no. 6, pp. 380-381, 2018.’Europe and C.d’Europe, “European Pharmacopoeiaâ€, 5th ed., Brussels: Council of Europe, 2004.

European Pharmacopoeia, “European Pharmacopoeiaâ€, Council of Europe, Brussels, Belgium, 2014.

M. Khan, T. Jabbar, M. Asif, M.I. Anjum, M. Dilband, K. Khan, A. Jabbar and W. Arshed, "Radiostrontium separation from sodium molybdate solution and its measurement using LSA: An application to radiopharmaceutical analysis", J. Radioanal. Nucl. Chem., vol. 299, no. 1, pp. 577-582, 2014.

S. Banerjee, M.R.A. Pillai and N. Ramamoorthy, "Evolution of Tc-99m in diagnostic radiopharmaceuticals Semin. Nucl. Med., vol. 31, no. 4, pp. 260-277, 2001.

M.U. Akbar, M.R. Ahmad, A. Shaheen and S. Mushtaq, "A review on evaluation of technetium-99m labeled radiopharmaceuticals", J. Radioanal. Nucl. Chem., vol. 310, no. 2, pp. 477-493, 2016.

M.D.S. Albernaz, S.H. Toma, J. Clanton, K. Araki and R. Santos-Oliveira, "Decorated superparamagnetic iron oxide nanoparticles with monoclonal antibody and diethylene-triamine-pentaacetic acid labeled with technetium-99m and galium-68 for breast cancer imaging", Pharm. Res., vol. 35, no. 1, pp. 24, 2018.

V.R. Solomon, C. Gonzalez, E. Alizadeh, W. Bernhard, S.V. Hartimath, K. Barreto, C.R. Geyer and H. Fonge, “99mTc (CO)3+ labeled domain I/II-specific anti-EGFR (scFv) 2 antibody fragment for imaging EGFR expression", Eur. J. Med. Chem., vol. 157, pp. 437-446, 2018.

C. Cerqueira-Coutinho, S. Missailidis, J. Alessandra-Perini, D.E. Machado, J.A. Perini and R. Santos-Oliveira, "Comparison of biodistribution profile of monoclonal antibodies nanoparticles and aptamers in rats with breast cancer", Artif. Cells Nanomed. Biotechnol., vol. 45, no. 3, pp. 598-601, 2017.

S. Mirzadeh, L.F. Mausner and M.A. Garland, Handbook of Nuclear Chemistry: Reactor-Produced Medical Radionuclides, 2nd ed., London: Springer Dordrecht, vol. 4., pp. 1857, 2011.

G.D. Luker, P.M. Fracasso, J. Dobkin and D. Piwnica-Worms, "Modulation of the multidrug resistance P-glycoprotein: detection with technetium-99m-sestamibi in vivo", J. Nucl. Med., vol. 38, no. 3, pp. 369-371, 1997.

T.R. Hayes, “Technetium-99m carbonyl complexes and new ligand development for targeted radiopharmaceuticalsâ€, Roseland, ProQuest LLC, 2016.

H.F. Kung, H.J. Kim, M.P. Kung, S.K. Meegalla, K. Plössl and H.K. Lee, "Imaging of dopamine transporters in humans with technetium-99m TRODATâ€, Eur. J. Nucl. Med., vol. 23, no. 11, pp. 1527-1530, 1996.

K. Zalewski, M. Benke, B. Mirocha, J. Radziszewski, M. Chechlinska and M. Kowalewska, "Technetium-99m-based radiopharmaceuticals in sentinel lymph node biopsy: gynecologic oncology perspective", Curr. Pharm. Des., vol. 24, no. 15, pp. 1652-1675, 2018.

D. Beiki, G. Yousefi, B. Fallahi, M.N. Tahmasebi, A. Gholamreza nezhad, A. Fard-Esfahani, M. Erfani and M. Eftekhari, "99mTc-Ubiquicidin, a promising radiopharmaceutical to differentiate orthopedic implant infections from sterile inflammation", Iran J. Pharm. Res., vol. 12, no. 2, pp. 347-353, 2013.

M.T. Ahmed, S.A.R. Naqvi, R. Rasheed, A.F. Zahoor, M. Usman and Z. Hussain, "Technetium-99m-labeled sulfadiazine: A targeting radiopharmaceutical for scintigraphic imaging of infectious foci due to escherichia coli in mouse and rabbit models", Appl. Biochem. Biotechnol., vol. 183, no. 1, pp. 374-384, 2017.

R. Bartosch, S. Granegger and H. Sinzinger, "Adsorption of technetium-99m tetrofosmin and technetium-99m furifosmin on plastic syringes", Eur. J. Nucl. Med., vol. 25, no. 9, pp. 1333-1335, 1998.

P.Z. Stavrou, M. Papachristou, E. Persakis, K. Kouvelis and L.E. Datseris, "Residual activities of 99mTc-labelled radiopharmaceuticals in routine nuclear medicine practice", Nucl. Med. Commun., vol. 37, no. 6, pp. 658-663, 2016.

C.I. Pearce, J.P. Icenhower, R.M. Asmussen, P.G. Tratnyek, K.M. Rosso, W.W. Lukens and N.P. Qafoku, "Technetium stabilization in low-solubility sulfide phases: A review", ACS Earth Space Chem., vol. 2, no. 6, pp. 532-547, 2018.

M. Khan and W. Um, "Liquid scintillation counting methodology for 99Tc analysis: a remedy for radiopharmaceutical waste", Anal. Chem., vol. 87, no. 17, pp. 9054-9060, 2015.

R.J. Serne, J.V. Crum, B.J. Riley and T.G. Levitskaia, Options for the separation and immobilization of technetium, Richland, WA (US): Pacific Northwest National Laboratory (PNNL), 2016.

S.A. Saslow, W. Um, C.I. Pearce, M.H. Engelhard, M.E. Bowden, W. Lukens and I.I. Leavy, "Reduction and simultaneous removal of 99Tc and Cr by Fe(OH)2(s) mineral transformation", Environmental science & technology, vol. 51, no. 15, pp. 8635-8642, 2017.

R. Koivula and R. Harjula, "Selective sorption of technetium on antimony-doped tin dioxide", Sep. Sci. Technol., vol. 46, no. 2, pp. 315-320, 2010.

E. Yalçıntaş, A.C. Scheinost, X. Gaona and M. Altmaier, "Systematic XAS study on the reduction and uptake of Tc by magnetite and mackinawite", Dalton Trans., vol. 45, no. 44, pp. 17874-17885, 2016.

A.D. Nunn, Radiopharmaceuticals: Chemistry and Pharmacology, CRC Press, 1992.

Y. Arano, “Recent advances in 99mTc radiopharmaceuticals’’, Ann. Nucl. Med., vol. 16, pp. 79-93, 2002.

J.E. Beaver and H.B. Hupfh, “Production of 99mTc on a medical cyclotron: A feasibility study", J. Nucl. Med., vol. 12, pp. 739-741, 1971.

M. Piramoon and S.J. Hosseinimehr, "The past, current studies and future of organometallic 99mTc(CO)3 labeled peptides and proteins", Curr. Pharm. Des., vol. 22, no. 31, pp. 4854-4867, 2016.

S.M. Qaim, ''Nuclear data for medical applications: an overview'', Radiochim. Acta, vol. 189, no. 89, pp. 4-5, 2001.

S.M. Qaim, "Nuclear data for medical radionuclides", J. Radioanal. Nucl. Chem., vol. 305, no. 1, pp. 233-245, 2015.

S.M. Qaim, "Nuclear data for production of new medical radionuclides", J. Nucl. Sci. Technol., vol. 39, no. 2, pp. 1272-1277, 2002.

J. Esposito, G. Vecchi, G. Pupillo, A. Taibi, L. Uccelli, A. Boschi and M. Gambaccini, "Evaluation of 99mTc and productions based on a high-performance cyclotron", Science and Technology of Nuclear Installations, 2013.

S.M. Qaim, S. Sudár, B. Scholten, A.J. Koning, and H.H. Coenen, "Evaluation of excitation functions of 100Mo(p, d+ pn) 99Mo and 100Mo (p, 2n) 99mTc reactions: estimation of long-lived Tc-impurity and its implication on the specific activity of cyclotron-produced 99mTc", Appl. Radiat. Isot., vol. 85, pp. 101-113, 2014. 55.

K. Gagnon, F. Bénard, M. Kovacs, T.J. Ruth, P. Schaffer, J.S. Wilson and S.A. McQuarrie, "Cyclotron production of 99mTc: Experimental measurement of the 100Mo (p, x) 99Mo, 99mTc and 99gTc excitation functions from 8 to 18 MeV", Nucl. Med. Biol., vol. 38, no. 6, pp. 907-916, 2011.

J. Tanguay, X. Hou, K. Buckley, P. Schaffer, F. Bénard, T.J. Ruth and A. Celler, "Quantitative analysis of relationships between irradiation parameters and the reproducibility of cyclotron-produced 99mTc yields", Phys. Med. Biol., vol. 60, no. 10, pp. 3883, 2015.

A. Dash, F.F.R. Knapp and M.R.A. Pillai, "99Mo/99mTc separation: An assessment of technology options", Nucl. Med. Biol., vol. 40, no. 2, pp. 167-176, 2013.

E.P. Horwitz and A.H. Bond, "Purification of radionuclides for nuclear medicine: the multicolumn selectivity inversion generator concept", Czechoslov. J. Phys., vol. 53, no. 1, pp. A713-A716, 2003.

S. Chattopadhyay, S.S. Das, M.K. Das and N.C. Goomer, "Recovery of 99mTc from Na2[99Mo] MoO4 solution obtained from reactor-produced (n, γ) 99Mo using a tiny Dowex-1 column in tandem with a small alumina column", Appl. Radiat. Isot., vol. 66, no. 12, pp. 1814-1817, 2008.

S.S. Jurisso, and J.D. Lydon, "Potential technetium small molecule radiopharmaceuticals", Chem. Rev., vol. 99, no. 9, pp. 2205-2218, 1999.

D. Singh, A.S. Wagh, M. Tlustochowicz and V. Mandalika, "Immobilization of fission products in low-temperature ceramic waste forms", Waste Management Symposia, 1997.

D. Singh, V.R. Mandalika, S.J. Parulekar and A.S. Wagh, "Magnesium potassium phosphate ceramic for 99Tc immobilization", J. Nucl. Mater., vol. 348, pp. 272-282, 2006.

R. Koivula and R. Harjula, "Selective sorption of technetium on antimony-doped tin dioxide", Sep. Sci. Technol., vol. 46, pp. 315-320, 2010.

J.S. McCloy, B.J. Riley, A. Goel, M. Liezers, M.J. Schweiger, C.P. Rodriguez, P. Hrma, D.S. Kim, W.W. Lukens and A.A. Kruger, "Rhenium solubility in borosilicate nuclear waste glass: Implications for the processing and immobilization of technetium-99", Environ. Sci. Technol., vol. 46, no. 22, pp. 12616-12622, 2012.

W. Um, H. Chang, J.P. Icenhower, W.W. Lukens, R. Jeffrey Serne, N. Qafoku, R.K. Kukkadapu and J.H. Westsik, "Iron oxide waste form for stabilizing 99Tc", J. Nucl. Mater., vol. 429, pp. 201-209, 2012.

K. Xu, P. Hrma, W. Um and J. Heo, "Iron phosphate glass for immobilization of 99Tc", J. Nucl. Mater., vol. 441, pp. 262-266, 2013.

T.A. Marshall, K. Morris, G.T.W. Law, J.F.W. Mosselmans, P. Bots, S.A. Parry and S. Shaw, "Incorporation and retention of 99-Tc(IV) in magnetite under high pH conditions", Environ. Sci. Technol., vol. 48, pp. 11853-11862, 2014.

S.A. Luksic, B.J. Riley, M. Schweiger and P. Hrma, "Incorporating technetium in minerals and other solids: A review", J. Nucl. Mater., vol. 466, pp. 526-538, 2015.

M.S. Lee, W. Um, G. Wang, A.A. Kruger, W.W. Lukens, R. Rousseau and V.A. Glezakou, "Impeding 99Tc(IV) mobility in novel waste forms", Nat. Commun., vol. 7, pp. 1-6, 2016.

J. Li, C. Chen, R. Zhang and X. Wang, "Reductive immobilization of Re(VII) by graphene modified nanoscale zero-valent iron particles using a plasma technique", Sci. China Chem., vol. 59, no. 1, pp. 150-158, 2016.

M.C. Stennett, T.H. Lee, D.J. Bailey, E.V. Johnstone, J. Heo and N.C. Hyatt, "Ceramic immobilization options for technetium", MRS Adv., vol. 21, no. 13, pp. 753-758, 2017.

R.M. Asmussen, C.I. Pearce, B.W. Miller, A.R. Lawter, J.J. Neeway, W.W. Lukens, M.E. Bowden, M.A. Miller, E.C. Buck, R.J. Serne and N.P. Qafoku, "Getters for improved technetium containment in cementitious waste forms", J. Hazard. Mater., vol. 341, pp. 238-247, 2012.

G. Wang, W. Um, D.S. Kim and A.A. Kruger, "99Tc immobilization from off-gas waste streams using nickel-doped iron spinel", J. Hazard. Mater., vol. 364, pp. 69-77, 2019.

L. Zhenyu, H. Yang, Y. Tao, H. Xin, L. Zhongyuan, L. Shuzhen and Z. Haibin, "Immobilization of solidified ceramic forms with magnesium phosphate cement", Ceram. Int., vol. 45, pp. 13164-13170, 2019.

M.S. Lee, S.A. Saslow, W. Um, D.S. Kim, A.A. Kruger, R. Rousseau and V.A. Glezakou, "Impact of Cr and Co on 99Tc retention in magnetite: A combined study of ab initio molecular dynamics and experiments", J. Hazard. Mater.,, vol. 387, pp. 121721, 2020.




How to Cite

M. Khan and Q. Mehmood, “Technetium-99m Radiopharmaceuticals: A Review on Basic and Applied Aspects”, The Nucleus, vol. 56, no. 4, pp. 163–171, Sep. 2020.