The ability of static and extremely low frequency (ELF) Magnetic Fields (MF) to interfere with neoplastic cell function has been evaluated. In vitro experiments were carried out to study the role of MF characteristics (intensity, frequency, and modulation) on two transformed cell lines (WiDr human colon adenocarcinoma and MCF-7 human breast adenocarcinoma) and one nontransformed cell line (MRC-5 embryonal lung fibroblast). Increase in cell death morphologically consistent with apoptosis was reported exclusively in the two transformed cell lines. Cell-death induction was observed with MF of more than 1 mT. It was independent of the MF frequency and increased when modulated MF (static with a superimposition of ELF at 50 Hz) were used. Based on the in vitro results, four different MF exposure characteristics were selected and used to treat nude mice xenografted with WiDr cells. The treatment of nude mice bearing WiDr tumors subcutaneously. with daily exposure for 70 min to MF for 4 weeks caused significant tumor growth inhibition (up to 50%) by the end of the treatment when modulated MF were used for at least 60% of the whole treatment period and the time-averaged total MF intensity was higher than 3.59 mT. No toxic morphological changes induced by exposure were observed in renewing, slowly proliferating, or static normal cells. A discussion on the possible biophysical mechanism at the base of the observed biological results is also offered.

The possibility that magnetic fields (MF) cause antitumor activity in vivo has been investigated. Two different experiments have been carried out on nude mice bearing a subcutaneous human colon adenocarcinoma (WiDr). In the first experiment, significant increase in survival time (31%) was obtained in mice exposed daily to 70 min modulated MF (static with a superimposition of 50 Hz) having a time average total intensity of 5.5 mT. In the second independent experiment, when mice bearing tumors were exposed to the same treatment for four consecutive weeks, significant inhibition of tumor growth (40%) was reported, together with a decrement in tumor cell mitotic index and proliferative activity. A significant increase in apoptosis was found in tumors of treated animals, together with a reduction in immunoreactive p53 expression. Gross pathology at necroscopy, hematoclinical/hematological and histological examination did not show any adverse or abnormal effects. Since pharmacological rescue of mutant p53 conformation has been recently demonstrated, the authors suggest that MF exposure may obtain a similar effect by acting on redox chemistry connected to metal ions which control p53 folding and its DNA-binding activity. These findings support further investigation aimed at the potential use of magnetic fields as anti-cancer agents.

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In an 18-month carcinogenicity study, Pim1 transgenic mice were exposed to pulsed 900 MHz (pulse width: 0.577 ms; pulse repetition rate: 217 Hz) radiofrequency (RF) radiation at a whole-body specific absorption rate (SAR) of 0.5, 1.4 or 4.0 W/kg [uncertainty (k = 2): 2.6 dB; lifetime variation (k = 1): 1.2 dB]. A total of 500 mice, 50 per sex per group, were exposed, sham-exposed or used as cage controls. The experiment was an extension of a previously published study in female Pim1 transgenic mice conducted by Repacholi et al. (Radiat. Res. 147, 631-640, 1997) that reported a significant increase in lymphomas after exposure to the same 900 MHz RF signal. Animals were exposed for 1 h/day, 7 days/week in plastic tubes similar to those used in inhalation studies to obtain well-defined uniform exposure. The study was conducted blind. The highest exposure level (4 W/kg) used in this study resulted in organ-averaged SARs that are above the peak spatial SAR limits allowed by the ICNIRP (International Commission on Non-ionizing Radiation Protection) standard for environmental exposures. The whole-body average was about three times greater than the highest average SAR reported in the earlier study by Repacholi et al. The results of this study do not suggest any effect of 217 Hz-pulsed RF-radiation exposure (pulse width: 0.577 ms) on the incidence of tumors at any site, and thus the findings of Repacholi et al. were not confirmed. Overall, the study shows no effect of RF radiation under the conditions used on the incidence of any neoplastic or non-neoplastic lesion, and thus the study does not provide evidence that RF radiation possesses carcinogenic potential.

Purpose The radiolabeled gastrin-releasing peptide receptor (GRPR)-targeting antagonist NeoB is a promising radioligand for imaging and therapy of GRPR-expressing malignancies. In the current study, we aimed to discover the target organs of toxicity and the radiotoxic effects to these organs, when repeated dosages of [177Lu]Lu-NeoB are administered to healthy female and male mice. Methods Animals received either 3 injections, with a 7-day interval, of vehicle (control group 1), 1200 pmol [175Lu]Lu-NeoB (control group 2) or 40 MBq/400 pmol, 80 MBq/800 pmol, and 120 MBq/1200 pmol [177Lu]Lu-NeoB (treatment groups 1, 2, and 3, respectively). At week 5, 19, and 43 after the first injection acute, early, and late organ toxicity, respectively, was determined. For this, histopathological and blood analyses were performed. To correlate the observed toxicity to absorbed dose, we also performed extensive biodistribution and dosimetry studies. Results The biodistribution study showed the highest absorbed doses in GRPR-expressing pancreas, the liver, and the kidneys (the main organs of excretion). Both control groups and almost all animals of treatment group 1 did not show any treatment-related toxicological effects. Despite the high absorbed doses, no clear microscopic signs of toxicity were found in the pancreas and the liver. Histological analysis indicated kidney damage in the form of hydronephrosis and nephropathy in treatment groups 2 and 3 that were sacrificed at the early and late time point. In the same groups, increased blood urea nitrogen levels were found. Conclusion In general, repeated administration of [177Lu]Lu-NeoB was tolerated. The most significant radiotoxic effects were found in the kidneys, similar to other clinically applied radioligands. The results of this study underline the potential of [177Lu]Lu-NeoB as a promising option for clinical therapy.