RT Journal Article
SR Electronic
T1 Evaluation of 68Ga/68Ge generator and preparation of a 68Ga-DOTA-hapten-peptide for bispecific antibody (bsMAb) pretargeting
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1526
OP 1526
VO 51
IS supplement 2
A1 Karacay, Habibe
A1 Sharkey, Robert
A1 McBride, Bill
A1 Chang, Chien-Hsing
A1 Goldenberg, David
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/1526.abstract
AB 1526 Objectives ImmunoPET imaging with an anti-CEACAM5 x anti-hapten (HSG) bsMAb pretargeting procedure is highly sensitive and specific for localizing colorectal cancer. We examined the preparation of high specific activity 68Ga-IMP 288, a di-HSG mono-DOTA-containing peptide, using a commercially available 68Ga/68Ge generator and its use for pretargeted PET imaging. Methods Eckert-Ziegler IGG-100 1.85 GBq gallium-68 generator was eluted with 0.1 M HCl in 3 fractions of 1.5, 1 and 2.5 mL. The 1-mL fraction contained 0.96 GBq at day 90 to 0.48 GBq 350 days after generator calibration. Optimal labeling occurred in 1.0 M HEPES buffer, pH 6.9, added at one-eighth the 68Ga volume, and then heated for 12 min in boiling water bath. Ascorbic acid added to the reaction mixture improved recovery and reduced radiolytic products, and DTPA was added to scavenge unbound 68Ga before purification on a Waters Oasis HLB cartridge. Results 68Ga-IMP 288 was prepared at a starting specific activity as high as 1.78 GBq/nmol, with final yields of 0.74 GBq/nmol following purification (decay corrected), with <1% unbound 68Ga. HLB purification was essential to remove unbound 68Ga and 68Ge breakthrough. High specific activity labeling (initial 0.89 GBq/nmol) could be performed even on day-350. 68Ga-IMP-288 was stable in vitro for at least 2 h at 25°C. Pretargeting in nude mice bearing LS174T human colonic cancer xenografts showed high 68Ga-IMP 288 uptake (27.5±5.8%ID/g), with high T/NT ratios (13.6±4.8, 66.8±14.5, and 325.9±61.9 for the kidney, liver, and blood, respectively) 1.5 h post-peptide injection. Conclusions High specific activity labeling of DOTA-containing peptide can be obtained from the 68Ga/68Ge-generator over a period of nearly 1 year, yielding products suitable for ImmunoPET imaging. Research Support Supported in part by SBIR grant 2R44CA123985-02A1 to C-HC and NJ CC grant 10-8-CCR-EO to RMS