manganese(iii)tetraphenylporphine-sulfonate and Brain-Neoplasms

A conjugate of manganese-metalloporphyrin and gadolinium (Gd)-diethylenetriaminepenta-acetic acid (Gd-ATN10) was developed as a tumor-specific enhancement agent for magnetic resonance (MR) imaging. Gd-ATN10 was evaluated in an experimental 9L gliosarcoma rat tumor model. T1-weighted MR imaging showed enhancement of the tumor which persisted for up to 24 hours. Gd concentration measurement by inductively coupled plasma atomic emission spectroscopy revealed the peak Gd concentration was reached after 30 minutes and Gd was retained in the blood and tumor up to 24 hours. There was no uptake of Gd in the normal brain and little in the skin. Gd-porphyrin derivatives are potentially useful agents for tumor diagnosis on MR imaging and for neutron capture therapy.

Topics: Animals; Brain; Brain Neoplasms; Contrast Media; Gadolinium DTPA; Gliosarcoma; Magnetic Resonance Imaging; Metalloporphyrins; Neoplasm Transplantation; Organometallic Compounds; Pentetic Acid; Rats; Rats, Inbred F344

The in vivo relaxation times T1 and T2 were quantitatively determined in rat brain. Animals with implanted experimental brain tumors were investigated for discrimination of pathological regions from normal brain structures based on relaxation time differences. The different cerebral tumors (glioma, schwannoma, neuroblastoma) showed no difference in relaxation times, but all tumors had T1(1301 +/- 167 ms) and T2(91 +/- 9 ms) times distinctly longer than normal brain (T1: 1057 +/- 77 ms; T2: 77 +/- 6 ms). T1 can be used for distinction of tumor and edema from normal brain, while T2 is the better parameter for discrimination between tumor and edema. Furthermore, the effect of MRI contrast agents (GdDTPA, MnTPPS, GdTPPS) on the relaxation times of these experimental brain tumors was measured. The enhancement of tumors produced by GdDTPA disappeared within ten minutes after i.p. application. At later times, central cysts and peritumoral edema became the most enhanced structures. The enhancement of tumor following MnTPPS application remained unchanged in T1-weighted images during the whole observation period of four days. A significant reduction of enhancement was not observed during this time. The effect of MnTPPS on T2 was weak. Replacement of manganese with gadolinium as the central ion of the porphyrin TPPS led to a contrast agent with enhancement effects on both, T1- and T2-weighted images.

Topics: Analysis of Variance; Animals; Brain Edema; Brain Neoplasms; Contrast Media; Diagnosis, Differential; Gadolinium; Gadolinium DTPA; Glioma; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Manganese; Metalloporphyrins; Neurilemmoma; Neuroblastoma; Organometallic Compounds; Pentetic Acid; Rats; Rats, Inbred F344; Tumor Cells, Cultured

The ultrafast inversion recovery snapshot FLASH technique was used to determine the kinetics of the contrast agent manganese (III) tetraphenylporphine sulfonate (MnTPPS) in experimental brain tumors in rats. In the first part of the investigation this technique was validated with the conventional inversion recovery spin-echo method by comparing in vivo T1 data of a normal rat brain. Agreement between T1 values obtained from both techniques was complete, as tested for a large number of pixels in identical coronal slices. In the second part the fast IR snapshot FLASH method was applied to study the effect of the NMR contrast agent MnTPPS on the T1 relaxation time of experimental gliomas in rat brains. T1 of normal brain tissue (1024-1035 ms), tumor (1217 ms), and edema (1199 ms) was determined with the inversion recovery version of the snapshot FLASH imaging technique. After intraperitoneal injection of MnTPPS (0.25 mmol/kg body wt) T1 decreased exponentially to 56% of control in tumor and to 62% in muscle. In normal and edematous brain tissue no significant changes in T1 were observed up to 5 h after injection of the contrast agent. Once the T1 contrast between tumor and peritumoral brain tissue had reached a saturation, the enhancement persisted for several hours to days. Therefore application of this contrast agent resulted in a sharp demarcation between glioma and peri-tumoral edema.

Topics: Animals; Brain; Brain Edema; Brain Neoplasms; Contrast Media; Glioma; Half-Life; Injections, Intraperitoneal; Magnetic Resonance Imaging; Male; Manganese; Metalloporphyrins; Models, Structural; Neck Muscles; Rats; Rats, Inbred F344; Temporal Muscle; Time Factors

Two cases of stereotactically induced and spontaneously metastasizing neoplasms in the rat and the cat brain are reported. In the rat, a malignant Schwannoma derived from initially supratentorially implanted RN6 cells developed a second tumor in the posterior cranial fossa. In the cat, a highly malignant polymorphous anaplastic glioma induced by implantation of cloned rat glioma cells (F98) into the left internal capsule developed small tumor cell nests along the ependyma of the ipsilateral ventricle. In precontrast magnetic resonance imaging (MRI) of both cases, the primary tumor was detectable only by a very weak hypointensity and through a shift of the midline. No metastases were apparent. Application of the metallated paramagnetic porphyrin derivative manganese(III) tetraphenylporphine sulfonate (MnTPPS) resulted in a remarkable contrast enhancement between tumoral and normal tissue, which was evident not only in the primary tumor but also in the small metastases. These observations demonstrate for the first time that MnTPPS is an efficient MRI contrast agent for the detection of metastases from primary brain neoplasms and, in consequence, support the hypothesis of its selective binding to tumor cells.

Topics: Animals; Brain Neoplasms; Cats; Contrast Media; Female; Glioma; Magnetic Resonance Imaging; Male; Manganese; Metalloporphyrins; Neoplasm Metastasis; Neoplasm Transplantation; Neurilemmoma; Rats; Rats, Inbred F344; Stereotaxic Techniques

In the experimental F98 rat glioma model the nuclear magnetic resonance contrast agent MnTPPS was used to increase the contrast between tumour and peritumourous brain tissue. By evaluating pre- and postcontrast CPMG echo trains after different dose and circulation times of MnTPPS, the transverse relaxation time T2, the magnetization extrapolated to the time zero M (0), and the contrast ratio Rc of the magnetizations in neoplastic and normal tissues were determined. According to these data a maximum contrast is obtained a few hours after injection of 0.25 mmol MnTPPS/kg bw, using spin echo pulse sequences with short repetition times TR (1,100 ms), and short spin echo time TE (25 ms).

Topics: Animals; Brain; Brain Neoplasms; Contrast Media; Glioma; Image Enhancement; Magnetic Resonance Spectroscopy; Metalloporphyrins; Neoplasm Transplantation; Rats; Rats, Inbred F344