Category Archives: Cancer

Combined Hyperthermia and Photodynamic Therapy Using a Sub-THz Gyrotron as a Radiation Source

Some researcher may think that using a gyrotron for DNP-NMR spectroscopy seems to be a very exotic application. This article describes another application that is up to now rather unusual – heating up cancer tissue for cancer treatment.

Miyoshi, N., et al., Combined Hyperthermia and Photodynamic Therapy Using a Sub-THz Gyrotron as a Radiation Source. J Infrared Milli Terahz Waves, 2016: p. 1-10.

http://dx.doi.org/10.1007/s10762-016-0271-z

In this paper, we present results of a hyperthermia treatment of malignant tumors using a gyrotron as a radiation source for heating of the cancerous tissue. They clearly demonstrate the efficiency of the irradiation by sub-THz waves, which leads to steady decrease of the volume of the tumor and finally to its disappearance. A combination of hyperthermia and photodynamic therapy (PDT) that utilizes a novel multifunctional photosensitizer has also been explored. In the latter case, the results are even more convincing and promising. In particular, while after a hyperthermia treatment sometimes a regrowth of the tumor is being observed, in the case of combined hyperthermia and PDT such regrowth has never been noticed. Another combined therapy is based on a preheating of the tumor by gyrotron radiation to temperatures lower than the hyperthermia temperature of 43 °C and followed then by PDT. The results show that such combination significantly increases the efficiency of the treatment. We consider this phenomenon as a synergy effect since it is absent when hyperthermia and PDT are applied separately, and manifests itself only when both methods are combined.

The use of dynamic nuclear polarization 13C-pyruvate MRS in cancer

Gutte, H., et al., The use of dynamic nuclear polarization 13C-pyruvate MRS in cancer. Am J Nucl Med Mol Imaging 2015. 5(5): p. 548-560.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620180/pdf/ajnmmi0005-0548.pdf

In recent years there has been an immense development of new targeted anti-cancer drugs. For practicing precision medicine, a sensitive method imaging for non-invasive, assessment of early treatment response and for assisting in developing new drugs is warranted. Magnetic Resonance Spectroscopy (MRS) is a potent technique for non-invasive in vivo investigation of tissue chemistry and cellular metabolism. Hyperpolarization by Dynamic Nuclear Polarization (DNP) is capable of creating solutions of molecules with polarized nuclear spins in a range of biological molecules and has enabled the real-time investigation of in vivo metabolism. The development of this new method has been demonstrated to enhance the nuclear polarization more than 10,000-fold, thereby significantly increasing the sensitivity of the MRS with a spatial resolution to the millimeters and a temporal resolution at the subsecond range. Furthermore, the method enables measuring kinetics of conversion of substrates into cell metabolites and can be integrated with anatomical proton magnetic resonance imaging (MRI). Many nuclei and substrates have been hyperpolarized using the DNP method. Currently, the most widely used compound is 13C-pyruvate due to favoring technicalities. Intravenous injection of the hyperpolarized 13C-pyruvate results in appearance of 13C-lactate, 13C-alanine and 13C-bicarbonate resonance peaks depending on the tissue, disease and the metabolic state probed. In cancer, the lactate level is increased due to increased glycolysis. The use of DNP enhanced 13C-pyruvate has in preclinical studies shown to be a sensitive method for detecting cancer and for assessment of early treatment response in a variety of cancers. Recently, a first-in-man 31-patient study was conducted with the primary objective to assess the safety of hyperpolarized 13C-pyruvate in healthy subjects and prostate cancer patients. The study showed an elevated 13C-lactate/13C-pyruvate ratio in regions of biopsy-proven prostate cancer compared to noncancerous tissue. However, more studies are needed in order to establish use of hyperpolarized 13C MRS imaging of cancer.

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate

Nelson, S.J., et al., Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate. Sci Transl Med, 2013. 5(198): p. 198ra108.

http://www.ncbi.nlm.nih.gov/pubmed/23946197

This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-(1)(3)C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo (1)(3)C MR data, it is possible to evaluate the distribution of agents such as [1-(1)(3)C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-(1)(3)C]lactate in tumor, with the ratio of [1-(1)(3)C]lactate/[1-(1)(3)C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect (1)(3)C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-(1)(3)C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-(1)(3)C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-(1)(3)C]lactate/[1-(1)(3)C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.

Metabolic Imaging by Hyperpolarized 13C Magnetic Resonance Imaging for In vivo Tumor Diagnosis

Golman, K., R.I. Zandt, M. Lerche, R. Pehrson, and J.H. Ardenkjaer-Larsen, Cancer research, 66, (2006)

http://www.ncbi.nlm.nih.gov/pubmed/17108122

The “Warburg effect,” an elevation in aerobic glycolysis, may be a fundamental property of cancer cells. For cancer diagnosis and treatment, it would be valuable if elevated glycolytic metabolism could be quantified in an image in animals and humans. The pyruvate molecule is at the metabolic crossroad for energy delivery inside the cell, and with a noninvasive measurement of the relative transformation of pyruvate into lactate and alanine within a biologically relevant time frame (seconds), it may be possible to quantify the glycolytic status of the cells. We have examined the metabolism after i.v. injection of hyperpolarized (13)C-pyruvate in rats with implanted P22 tumors. The strongly enhanced nuclear magnetic resonance signal generated by the hyperpolarization techniques allows mapping of pyruvate, lactate, and alanine in a 5 x 5 x 10 mm(3) imaging voxel using a 1.5 T magnetic resonance scanner. The magnetic resonance scanning (chemical shift imaging) was initiated 24 seconds after the pyruvate injection and had a duration of 14 seconds. All implanted tumors showed significantly higher lactate content than the normal tissue. The results indicate that noninvasive quantification of localized Warburg effect may be possible.

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