EPR Tumor Oximetry With CE India Ink

It has been well established that malignant tumors tend to have low levels of oxygen and that tumors with very low levels of oxygen are more resistant to radiotherapy and other treatments, such as chemotherapy and immunotherapy. Previous attempts to improve response to therapy by increasing the oxygen level of tissues have had disappointing results and collectively have not led to changing clinical practice. Without a method to measure oxygen levels in tumors or the ability to monitor over time whether tumors are responding to methods to increase oxygen during therapy, clinician's reluctance to use oxygen therapy in usual practice is not surprising. The hypothesis underlying this research is that repeated measurements of tissue oxygen levels can be used to optimize cancer therapy, including combined therapy, and to minimize normal tissue side effects or complications. Because studies have found that tumors vary both in their initial levels of oxygen and exhibit changing patterns during growth and treatment, we propose to monitor oxygen levels in tumors and their responsiveness to hyperoxygenation procedures. Such knowledge about oxygen levels in tumor tissues and their responsiveness to hyper-oxygenation could potentially be used to select subjects for particular types of treatment, or otherwise to adjust routine care for patients known to have hypoxic but unresponsive tumors in order to improve their outcomes. The overall objectives of this study are to establish the clinical feasibility and efficacy of using in vivo electron paramagnetic resonance (EPR) oximetry-a technique related to magnetic resonance imaging (MRI)-to obtain direct and repeated measurements of clinically useful information about tumor tissue oxygenation in specific groups of subjects with the same types of tumors, and to establish the clinical feasibility and efficacy of using inhalation of enriched oxygen to gain additional clinically useful information about responsiveness of tumors to hyper-oxygenation. Two devices are used: a paramagnetic charcoal suspension (Carlo Erba India ink) and in vivo EPR oximetry to assess oxygen levels. The ink is injected and becomes permanent in the tissue at the site of injection unless removed; thereafter, the in vivo oximetry measurements are noninvasive and can be repeated indefinitely.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Subject must be capable of giving informed consent or has an acceptable surrogate capable of giving consent on behalf of the subject.
2. Subject has an eligible tumor that is within 5 mm of the surface (either skin or mucosa) or has had a tumor removed with a tumor bed that is within 5 mm of the surface.

   1. Eligible tumors types:

      * Intraoral tumors: squamous cell carcinoma (SCC), melanoma;
      * Primary cutaneous tumors (including, but not limited to): SCC, basal cell carcinoma (BCC,) melanoma;
      * Breast malignancies post surgery;
      * Other tumors: any tumor within 5 mm of the surface and with planned radiation therapy.

Exclusion Criteria:

1. Previous adverse reaction to a charcoal product e.g., a local hypersensitive response from a black tattoo or from ingestion of activated charcoal
2. Previous adverse reaction to the suspending agent
3. Subject has a pacemaker that is not known to be MRI compatible
4. Subject has a non-removable implant or device with metal that is not known to be MRI compatible
5. Subject is pregnant or has a likelihood for becoming pregnant during the basic study timeframe.

Note: There is no known harm to the woman or her fetus from participating; this is precautionary only.

• BACKGROUNDBacic G, Liu KJ, O'Hara JA, Harris RD, Szybinski K, Goda F, Swartz HM. Oxygen tension in a murine tumor: a combined EPR and MRI study. Magn Reson Med. 1993 Nov;30(5):568-72. doi: 10.1002/mrm.1910300507. PMID 8259056
• BACKGROUNDBaudelet C, Gallez B. How does blood oxygen level-dependent (BOLD) contrast correlate with oxygen partial pressure (pO2) inside tumors? Magn Reson Med. 2002 Dec;48(6):980-6. doi: 10.1002/mrm.10318. PMID 12465107
• BACKGROUNDBrizel DM, Scully SP, Harrelson JM, Layfield LJ, Dodge RK, Charles HC, Samulski TV, Prosnitz LR, Dewhirst MW. Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas. Cancer Res. 1996 Dec 1;56(23):5347-50. PMID 8968082
• BACKGROUNDBrizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):285-9. doi: 10.1016/s0360-3016(97)00101-6. PMID 9226314
• BACKGROUNDCharlier N, Beghein N, Gallez B. Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR. NMR Biomed. 2004 Aug;17(5):303-10. doi: 10.1002/nbm.902. PMID 15366029
• BACKGROUNDChaplin DJ, Horsman MR. Tumor blood flow changes induced by chemical modifiers of radiation response. Int J Radiat Oncol Biol Phys. 1992;22(3):459-62. doi: 10.1016/0360-3016(92)90853-a. PMID 1735678
• BACKGROUNDDardzinski BJ, Sotak CH. Rapid tissue oxygen tension mapping using 19F inversion-recovery echo-planar imaging of perfluoro-15-crown-5-ether. Magn Reson Med. 1994 Jul;32(1):88-97. doi: 10.1002/mrm.1910320112. PMID 8084241
• BACKGROUNDDemidenko E. Mixed models: theory and applications with R. John Wiley & Sons; 2013 Aug 26.