Tissue distribution and stability of metalloporphyrin MRI contrast agents

Abstract

Mn(III), Fe(III), and Gd(III) complexes of tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and several other porphyrins were evaluated as potential MRI contrast agents. Based on consideration of relaxivity and stability properties in solution, MnTPPS was found to be the compound of choice. At pH 7 the Gd and Mn complexes significantly enhanced the water proton relaxation rate, while the relaxivity of FeTPPS exhibited a significant loss of relaxivity above pH 6 due to oxy-dimer formation. Although GdTPPS exhibited the highest relaxivity in solution, this property was rapidly lost due to dissociation of the metal ion. By contrast MnTPPS remained stable in human plasma after incubation for 9 days. Upon intravenous injection into athymic mice bearing subcutaneous human colon carcinoma xenografts, MnTPPS provided enhanced relaxation of the tissue water in several excised mouse tissues, notably kidney, liver, and tumor. The results at a fixed field (0.25 T) and relaxation dispersion studies showed decreases in water relaxation rates with time for kidney and liver, but an increase for the tumor, with a maximum near 4 days at the highest dose used.

Noninvasive Measurements of Infarct Size After Thrombolysis With a Necrosis-Avid MRI Contrast Agent

“…Other studies with metalloporphyrins also suggest that these agents are stable compounds. 24 The only known toxic effects are skin discoloration and photosensitization due to uncomplexed porphyrins, 11 but these are reduced by chelation of a metal. The LD 50 of gadophrin-2 in rats is comparable with that of Gd-DTPA.…”

Selective enhancement of experimental rat brain tumors with Gd‐TPPS

“…In the same year, Lyon et al described Gd-TPPS as highly unstable, thus prohibiting its in vivo use (4). In 1988, we presented data showing Gd-TPPS to be a more effective relaxation accelerator at 20 MHz than Mn-TPPS or Gd-DTPA.…”

“…we found a distinctly smaller extinction at 510 nm than at 575 nm. In the observed range of 450-700 nm, unmetallated TPPS has its greatest absorption at about 510 nm (4). Therefore, we assume that our preparation of Gd-TPPS contained less TPPS than that described by Horrocks and Hove.…”

“…We, therefore, assume that Lyon et al used a Gd-TPPS derivative that did not include acetylacetonate in its structure. This assumption is supported by the carbon content (C44) those authors determined by means of elemental analysis (4).…”

MRI with Gadolinium‐Based Nanoparticles

“…Complexed in porphyrins, it exhibits high relaxivities and can be used to target various cancer cells. In this case, Mn 3+ is used advantageously over Gd 3+ because of the higher stabilities of the complexes formed, Gd 3+ being released from porphyrins in solution [187]. As a nanoparticle component, Mn 3+ porphyrins have been coupled to dextran to obtain macromolecular structures exhibiting tumor cell membrane affinity with relaxivities 50-75% higher than Gd 3+ -dTpA [188].…”