The Radiopharmaceutical Chemistry of Gallium(III) and Indium(III) for SPECT Imaging - The Chemistry of Molecular Imaging - page 176

111 In-NlS-DOTA-TOC (TOC = octreotide analogue) has 45 times more nuclear uptake than 111 In-DOTA-TOC [92]. An
alternative route to target the nucleus has been to use 111 In-EDTA conjugated to an antisense nucleotide sequence that was
encapsulated in a vesicle. This has been used as a potential therapy for neuroblastoma. The conjugate was shown to inhibit
tumour cell proliferation [93].
Antibodies have also been explored as the targeting vectors. 111 In-DTPA has been conjugated to the Hum195 antibody,
which binds to the transmembrane CD33 receptor. Addition of NlS to the antibody exterior significantly increased the
nuclear localisation and the cytotoxicity toward clonogenic tumour cells [94]. The antibody Trastuzumab (Herceptin) binds
to the HER2 protein and has also been decorated with NlS peptide and labelled with 111 In with the radioconjugate dramati-
cally decreasing clonogenic tumour cell survival [95, 96]. Two biological targeting molecules have proved more effective
than one in the radiolabelled conjugate 111 In-DTPA-RGD-octreotide, which shows enhanced tumour cell death relative to
111 In-DTPA-octreotide [30], [97]. Several of the conjugates described have been subjected to clinical trials, and the prospects
for Auger electron therapy are very positive. Doubtless there will be further advances in this area in the future, inclusively
alongside advances of nanomedicine and nanotechnology for medical imaging applications: indeed some recent work (2013)
led to the radiolabeling of nanographene oxide (NGO) with indium-111 and the simultaneous incorporation of trastuzumab.
Such nano-constructs (NGO-trastuzumab) when radiolabeled showed enhanced pharmacokinetics in vivo with respect to
indium-trastuzumab alone (i.e. in the absence of NGO) coupled with a rapid clearance from circulation and the promising
targeting of Her2 receptors [97].

7.4 prospects for 67 Ga and 111 In radIochemIstry

The relatively few papers covering SPECT imaging with 67 Ga and 111 In that have appeared in the last 10 years partly reflect
the pronounced shift toward PET imaging and apart perhaps for Ga citrate, 67 Ga has been superseded by 68 Ga. Without the
convenience of a generator system, it is difficult to envisage either 67 Ga or 111 In competing effectively with 99m Tc, let alone
PET radionuclides. The fundamental coordination chemistry of Ga and In lacks the diversity of Tc and Re, and the current
range of chelators appears to meet all the current radiopharmaceutical requirements. There is, therefore, not the driving force
of new coordination chemistry to stimulate the development of new SPECT agents. However, 111 In also offers the possibility
of highly effective targeted Auger electron therapy, and this would appear to be the area most likely to expand in the future
inclusively alongside recent developments in nanomedicine for imaging applications.

references

[1] m. D. Bartholomä, A. S. louie, J. F. Valliant and J. Zubieta, Chem. Rev. 110 , 2903-2920 (2010).
[2] S. Chakraborty and S. liu, Curr. Top. Med. Chem. 10 , 1113-1134 (2010).
[3] A. Signore, S. J. mather, G. Piaggio, G. malviya and R. A. Dierckx, Chem. Rev. 110 , 3112-3145 (2010).
[4] T. J. Wadas, E. H. Wong, G. R. Weisman and C. J. Anderson, Chem. Rev. 110 , 2858-2902 (2010).
[5] C. Edwards and R. Hayes, J. Nucl. Med. 10 , 103-104 (1969)
[6] C. Edwards and R. Hayes, J. Nucl. Med. 10 , 332-334 (1969).
[7] P. O'Brien, H. Salacinski and m. motevalli, J. Am. Chem. Soc. 119 , 12695-12696 (1997).
[8] C. l. Edwards and R. l. Hayes, J. Nucl. Med. 10 , 103-105 (1969).
[9] D. J. Berry, y. ma, J. R. Ballinger, R. Tavare, A. Koers, K. Sunassee, T. Zhou, S. Nawaz, G. E. D. mullen, R. C. Hider and P. J.
Blower, Chem. Commun. 47 , 7068-7070 (2011).
[10] S. Chaves, A. C. mendonca, S. m. marques, m. I. Prata, A. C. Santos, A. F. martins, C. F. G. C. Geraldes and m. A. Santos, J. Inorg.
Biochem. 105 , 31-38 (2011).
[11] y. Sun, C. Anderson, T. Pajeau, D. Reichert, R. Hancock, R. motekaitis, A. martell and m. Welch, J. Med. Chem. 39 , 458-470 (1996).
[12] m. loken, m. Clay, R. Carpenter, R. Boudreau and J. mcCullough, Clin. Nucl. Med. 10 , 902-911 (1985).
[13] W. Heaton, H. Davis, m. Welch, C. mathais J. Joist, l. Sherman and B. Siegel, British Journal of Haematology 42 , 613-622 (1979).
[14] C. mathais and m. Welch, J. Nucl. Med. 20 , 659-659 (1979).
[15] m. Green and J. Huffman, J. Nucl. Med. 29 , 417-420 (1988).
[16] C. Broan, J. Cox, A. Craig, R. Kataky, D. Parker, A. Harrison, A. Randall and G. Ferguson, J. Chem. Soc.-Perkin Trans. 2 87-99 (1991).
[17] J.-F. morfin and E. Toth, Inorg. Chem. 50 , 10371-10378 (2011).
[18] A. Craig, I. Helps, D. Parker, H. Adams, N. Bailey, m. Williams, J. Smith and G. Ferguson, Polyhedron 8 , 2481-2484 (1989).
[19] m. Green, m. Welch and J. Huffman, J. Am. Chem. Soc. 106 , 3689-3691 (1984).