Imaging of Transmetallation and Chelation Phenomena Involving Radiological Contrast Agents in Mineral-Rich Fruits

Abstract

Exogenous heavy metals or non-metallic waste products, for example lanthanide or iodinated contrast media for radiological procedures, may interfere with the biochemical pools in patients and in common food sources, creating an excess buildup of exogenous compounds which may reach toxic levels. Although the mechanisms are unknown, our experiments were designed to test if this toxicity can be attributed to "transmetallation" or "chelation" reactions freeing up lanthanides or chelated transition metals in acidic fruits used as phantoms representing the biologically active and mineral-rich carbohydrate matrix. The rapid breakdown of stable contrast agents have been reported at a lower pH. The interaction of such agents with native metals was examined by direct imaging of contrast infused fresh apples and sweet potatoes using low energy X-rays (40-44 kVp) and by magnetic resonance imaging at 1.5 and 3T. The stability of the exogenous agents seemed to depend on endogenous counterions and biometals in these fruits. Proton spin echo MR intensity is sensitive to paramagnetic minerals and low energy X-ray photons are sensitively absorbed by photoelectric effects in all abundant minerals and were compared before and after the infusion of radiologic contrasts. Endogenous iron and manganese are believed to accumulate due to interactions with exogenous iodine and gadolinium in and around the infusion spots. X-ray imaging had lower sensitivity (detection limit approximately 1 part in 10⁴), while MRI sensitivity was two orders of magnitude higher (approximately 1 part in 10⁶), but only for paramagnetic minerals like Mn and Fe in our samples. MRI evidence of such a release of metal ions from the native pool implicates transmetallation and chelation reactions that were triggered by infused contrast agents. Since Fe and Mn play significant roles in the function of metalloenzymes, our results suggest that transmetallation and chelation could be a plausible mechanism for contrast induced toxicity in vivo.

Keywords: GBCA; T1 and T2 relaxations; X-ray; chelation; contrast induced toxicity; environmental pollution; environmental toxins; gadolinium; iodinated contrast; magnetic resonance imaging; mammographic soft X-ray; radiological contrast media; transmetallation.

Figure 1

X-ray images of the mineral-rich apple at two different X-ray energies showing mineral conspicuity as a function of mean X-ray energy. (A) Non-contrast X-ray image at 40 kVp/10 mAs (with mean energy approx. 13 keV) using a clinical scanner; two typical high attenuation tracks marked by a white arrow indicate either K or Fe concentrated regions (Table 1). (B) Another apple slice showing the same mineral tracks at higher mineral conspicuity presumably due to lower kVp (soft) mammographic X-ray beam (20 kVp/10 mAs with mean energy approx 7 keV, close to k-edges of transition metal ions but far from k-edge of K ions, Table 1).

Figure 2

X-ray images of the mineral-rich model fruits and vegetables. 1st row: Cut samples: apple (left) and sweet potato (right) and manually carved holes (2 × 2 × 10 mm³ or 0.04 mL for apple and approx 3.3 × 3.3 × 20 mm³ or 0.2 mL for sweet potato). 2nd row: Pre-contrast X-ray images at 44 keV/15 mAs by a clinical scanner. 3rd row: Post-contrast X-ray images showing Gadavist is perfused in the left wells (white arrows) and Iohexol in the right wells (yellow arrows) for both fruits. 4th row: Molecular structures of both of the contrast media.

Figure 3

MR images of the mineral-rich model fruits and vegetables. First row: Pre-contrast MR image at 1.5T Siemens system, apple (left) and sweet potato (right). Manually carved wells (2 × 2 × 10 mm³ or 0.04 mL volume) are shown (white arrows). Second row: Post-contrast MR image when Gadavist is added at the left wells and Iohexol in the right wells for both fruits. Notice signal loss due to paramagnetic nature of Gd³⁺ and enhanced signal due to Iohexol. Third to fifth rows: Time series subtraction images (post-pre contrast) at time = 5 min, 35 min and 65 min are shown. More pronounced enhancement is seen with Iohexol in sweet potato.

Figure 4

High Field (3T) MR images of the mineral-rich apple (left) and sweet potato (right), each with two carved wells infused five days prior with iodinated contrasts Omnipaque (240, thin arrow and 350, thick arrow). Also shown is the image of a banana at the superior/middle aspect.