Radioiodination of antibodies via N-succinimidyl 2,4-dimethoxy-3-(trialkylstannyl)benzoates

Abstract

We have previously shown that use of N-succinimidyl 3-iodobenzoate (SIB) for radioiodination of monoclonal antibodies (MAbs) decreases the loss of radioiodine in vivo compared to MAbs labeled by using conventional methods. Herein, the synthesis of N-succinimidyl 2,4-dimethoxy-3-(trialkylstannyl)benzoates (alkyl = Me, Bu) are described as is their use as precursors for the radiosynthesis of N-succinimidyl 2,4-dimethoxy-3-iodobenzoate (SDMIB). A MAb F(ab')2 fragment labeled with SDMIB retained its ability to bind specifically to tumor homogenates. Paired-label tissue distribution studies indicate that the thyroid uptake (an indicator of deiodination) of hydrolyzed SDMIB was about 20 times that of hydrolyzed SIB. In contrast, thyroid uptake for SDMIB, when conjugated to a MAb, was only 1.4-2.8 times that for SIB and was considerably lower than levels reported in the literature for MAbs labeled by using direct, electrophilic iodination methods. Although MAbs labeled with SDMIB are significantly more inert to dehalogenation than those labeled by conventional methods, compared to the original SIB reagent, addition of two methoxy groups decreased retention of label in vivo.

SIB-DOTA: A trifunctional prosthetic group potentially amenable for multi-modal labeling that enhances tumor uptake of internalizing monoclonal antibodies

“…The lower conjugation yields, compared with SIB and substituted SIB analogues, 13, 37, 38 might be due partial hydrolysis of [ 131 I] 10 leaving less active ester available for conjugation. The integrity of the labeled mAb was evaluated by several methods.…”

Expression of HMP/AN2, a melanoma associated antigen, in murine cerebral gliomas: potential for radioimmunotargeting

“…Labeling of mAbs with 124 I was performed using a modification of the standard Iodogen method, as described previously [29]. The antibody solution (1mg/mL of PBS; 0.1 mL) was added to 10 μL of 124 I (1-5 mCi) in 0.1 N NaOH.…”

SPECT/CT Imaging of Mycobacterium tuberculosis Infection with [125I]anti-C3d mAb

“…At 24 h post-injection, 3D maximum intensity projections (MIPs) of healthy mice injected with [ 125 I]3d29 showed a small amount of uptake in the spleen (S) as well as in the thyroid (T) due to in vivo dehalogenation (Fig. 1a) of the radiolabeled antibody [18][19][20]. Otherwise, all other healthy tissue uptake was low (1.2 % ID/g).…”