SPECT Isotopes

For SPECT the isotope of choice is technetium-99m (99mTc) because of its ideal physical properties (pure gamma-emitting decay, imaging equipment-matched energy, short half-life of 6h). The generator-based radioisotope production technology is convenient and cost-saving. Established chelators allowing for 99mTc labeling are HYNIC, MAG2 (N3S systems), or MAG3, which have already been used successfully for labeling of antisense oligonucleotides and RNA-aptamers

Table 16.6 Common SPECTand PET isotopes with physical half-lives and labeling methods

Isotope Half-life Modality Labeling/Chelator/Precursor nTc

SPECT e.g. MAG3

or peptidergic chelator Glv_/

SPECT PET

mIn

67.3 h

SPECT

68Ga

68 min

PET

64Cu

12.7 h

lodination of e.g. stannyl phosphoramidite

or bromoacetamide o

Labeling by metal complexation of e.g. DPTA or DOTA

ho2c co2h co2h

SF two-step labeling of e.g. fliiorobenzylbromoacetamide or succinimidofluorobenzoate o o

"W

"W

,8F)SFB

(Table 16.6). High conjugation yields and high specific activities can be achieved in a reproducible and robust manner. Typical 99mTc-radiolabeling efficiencies reported for MAG3 and HYNIC antisense-DNA oligonucleotides were 40% and 60%, respectively with a specific activity of ~85 MBq/nmol (Zhang et al., 2000). MAG3 was also used for 3' end labeling of a 20-mer antisense oligonucleotide aminohexyl derivative. Tc-99m labeling yielded 32-35% with >90% purity and a specific activity of 14.9GBq/mg (Hjelstuen et al., 1998). A MAG2-amide RNA aptamer could be labeled with 99mTc with a 95% radiochemical yield and a specific activity of 37 MBq/nmol (Hilger et al., 1998). Comparable results (>95% purity, 40-80% radiochemical yield, specific activity 14.8-29.6 MBq/mg) were achieved by labeling the stabilized tenascin-C targeting RNA aptamer TTA1 and its 2'-O-methyl and LNA analogs via a MAG2 chelator (Schmidt et al., 2004).

Indium-111 labeling is pursued either via attaching bifunctional DTPA or DOTA chelators to the aptamer. Iodine-123 or iodine-125 labeling of aptamers can be achieved by indirect iodination. Methods for radioiodination of stannyl-oli-gonucleotides (DNA aptamers against human thrombin) reported by Dougan et al. (1997) using chloramine-T, iodogen, and iodobeads resulted reproducibly in yields >90%. Specific activities of 37-74 GBq/nmol for 125I and >185 GBq/nmol for 123I were achieved with the same oligonucleotides (Dougan et al., 2003). The yields and specific activities achieved with the aforementioned labeling methods are sufficient to make use of radiolabeled antisense oligonucleotides or aptamers in preclinical and clinical SPECT imaging.

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