Figure 1.
Charge distribution of 2-(4-iodo-phenethyl)-malonic acid (IPM) at pH 7 (2 negative charges) and at pH 6 (the compound contains only one negative charge, which is distributed over the malonate moiety).
Given that the highest pKa value for IPM is 5.78, a significant portion of the compound is in this state at pH 6, allowing passive diffusion over a cell membrane. The lower part of the figure depicts the structure of 2-(4-iodo-phenethyl)-malonic acid (IPM), 2-(4-iodo-phenethyl)-2-methyl-malonic acid (IPMM), 2-(4-iodo-benzyl)-2-methyl-malonic acid (IBMM) and 4-iodo-phtalic acid (IP).
Figure 2.
Exemplary UV- (top) and radiochromatogram (bottom) of reaction mixture after radioiodination of IPMM (60 min reaction time, 90°C, 1 mg precursor).
In the UV signal, gentisic acid (Rt: 10 min), IPMM (Rt: 15 min) and IPMM diethyl ester (Rt: 16 min) can be identified. In the radiochromatogram, 123I-labeled IPMM and 123I-labeled IPMM diethyl ester can be seen, as well as an unidentified side compound (Rt: 7 min).
Figure 3.
Uptake of 123I-labeled IPMM, IBMM, IP and IPM in Jurkat cells in control conditions, with anti-fas mAb induced apoptosis, incubated in KCl-solution and with freeze-thaw induced necrosis.
Figure 4.
Uptake of 123I-labeled IPM in Jurkat cells after 3 h incubation in phosphate buffered NaCl or phosphate buffered KCl solutions as a function of in situ pH.
The [IPM−/[IPM2−] ratio is shown for comparison (dotted line).
Figure 5.
Biodistribution of 123I-labeled IPMM and IPM in healthy NMRI mice, 60 min p.i.
Figure 6.
SPECT/CT image of [123I]-labeled IPM in healthy NMRI mice, acquired between 45–80 min p.i. (summed image).
(A) Coronal section of the mouse body (head not included), showing high uptake in bladder and heart (blood pool). (B) Transversal section of the mouse in the heart region. (C) Transversal section showing bladder activity.
Figure 7.
pH dependency of tumor uptake.
Autoradiographic images of tumor slices from untreated (A) and treated (B) (hyperglycemia + MIBG) mice. (C) and (D) are caspase-3 stainings of respective tumor tissues. The table indicates pH, [IPM-]/[IPM2−] ratio at indicated pH and the uptake of the tracer, expressed as %ID/g.