Radiofrequency hyperthermia with successive monitoring of its effects on tumors using NMR spectroscopy.

Abstract

Radiofrequency (rf) hyperthermia was generated on rat glioma inoculated s.c. in CD Fisher rats by applying the rf pulse using the surface coil in the NMR spectrometer, and the effect was monitored successively in the same spectrometer by measuring 31p NMR spectra and 'H NMR images. In the 31P NMR spectrum at the preirradiation stage, nucleoside triphosphate peaks and a phosphomonoester peak were high and a Pi peak was low. After a rf pulse at a power of 5 W was applied continuously for 60 min, the nucleoside triphosphate peaks decreased and the Pi peak increased immediately, resulting finally in a dominant Pi peak pattern within 30 min in all 10 cases ened. These spectral changes occurred much earlier than the histological changes and lasted for at least 7 days. By the 1H NMR imaging, the necrotic region was detected as a high-intensity lesion in spin echo and inversion recovery images 2 days after the irradiation. There were no changes either in the spectrum or in 1H NMR images in any of 8 cases after irradiation with a rf pulse of <3 W. Thus, we could generate rf hyperthermia with the NMR spectrometer and the effects were monitored sensitively with the same spectrometer. It can be concluded that the NMR device can be used not only for diagnosis but also. as a therapeutic tool.Radiofrequency (rf) hyperthermia is a matter of concern in cancer treatment (1). Though the mechanism and effects of this therapy have been studied extensively, many problems have been left unsolved-for example, the appropriate power of the rf pulse, proper duration of heating, proper design of the rf coil, effectiveness ofcombined therapy, and so on. This is partly due to the lack of an appropriate method for examining the mechanism and for evaluating the effect of the treatment in vivo. Meanwhile, there has been recent, rapid progress in the application ofNMR to the medical field. In the course of looking for new applications ofthe NMR method to the medical field, we took notice of generating rf hyperthermia using a NMR spectrometer. As a NMR spectrometer transmits a rf pulse, it should be possible to produce hyperthermia using the rf pulse generated by the spectrometer in the magnet. It is also supposed that the effects so produced could be monitored sensitively with the same spectrometer by 31P NMR spectrum measurements as in other therapies (2)(3)(4)(5). Therefore, we intended to generate rf hyperthermia on experimental tumors using the NMR spectrometer with successive monitoring of the effects in the same device in an attempt to find a further application of NMR as well as to obtain informative data for hyperthermia as a cancer therapy. MATERIALS AND METHODSExperimental Animals. A total of 54 CD Fisher rats was used for the experiments. A suspension of 106_107 cultured rat glioma (EA285) cells was inoculated s.c. in the lumbar region of the animal (2). Twenty-eight days after inoculating the tumor cells, when the tumors grew to >1.5 cm in diameter, the animals were divided into two groups-a control group and the rf hyperther...

Hetergeneous tumour response to photodynamic therapy assessed by in vivo localised 31P NMR spectroscopy

“…At 24 h after PDT irradiation, the level E P-NTP/Pi ratios remained significantly reduced compared to all pre-treatment control levels. Inter- (Figure 6), followed by a gradual return to near pretreatment levels by [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] h, a finding which is in agreement with other investigators (Naruse et al, 1986b;Chopp et al, 1987Chopp et al, , 1990 (Ceckler et al, 1986;Hilf et al, 1987 (Gibson et al, 1990).…”

Controlled radio-frequency hyperthermia using an MR scanner and simultaneous monitoring of temperature and therapy response by1H,23Na and31P magnetic resonance spectroscopy in subcutaneously implanted 9L-gliosarcoma

“…In vivo 31 P NMR experiments show that HT produced an irreversible 40% decrease in NTP/P i at the end of HT whereas pH i and pH e showed reversible decreases by $0.2 pH units during HT. These changes in cellular energy status and pH in the 9L gliosarcoma model are smaller compared to that reported for sc-implanted RIF-1 tumours [5,12,13,15] perhaps because of differences in the two tumour models. Previous HT studies on sc-implanted C6 glioma (13) and perfused gliosarcoma cells (11) also showed small changes in tumour pH (0.2 units) as reported here.…”

“…The use of the same MR spectrometer with its components for RF heating as well as to excite spins to perform MR data collection was first proposed by Naruse et al [13]. In their study, they delivered RF HT to a sc-implanted tumour model in rat by applying continuous RF power to a surface coil.…”

“…Temperature can also influence pH considerably due to changes in energy metabolism. A decrease in the nucleosidetri-phosphates (NTP), and an increase in inorganic phosphate (P i ) levels, as well as the intracellular pH (pH i ) shifting towards the acidic state, are some of the responses exhibited with HT treatment monitored using 31 P NMR [9,[12][13][14][15]. Monitoring cellular metabolic response during HT treatment may be more reliable in assessing therapy efficacy than monitoring temperature alone because different tumours and tumour regions may have different vulnerabilities to heat.…”

State of Art on Bioimaging by Nanoparticles in Hyperthermia and Thermometry: Visualization of Tissue Protein Targeting

“…Other potential hyperthermic particles are silver, iron, zinc and lanthanum nanoparticles [46]. Presently, colloidal gold particles are used in monitoring metabolic changes as bound with antibodies, lipids during cellular uptake and endocytosis [47,48]. Carbon nanotubes were reported in thermal ablation of malignant tissue with DNA encaged carbon nanotubes [49].…”