The Washington State Life Sciences Discovery Fund, in cooperation with Vivos Inc., is sponsoring an animal “clinical trial” at Washington State University’s College of Veterinary Medicine (Pullman) and College of Pharmacy (Spokane).  While many pre-clinical studies involve animals that are purchased and deliberately implanted with tumor tissue for research purposes, this study represents a clinical trial in the sense that subjects are actual cat patients with spontaneous sarcomas that have been referred to the Veterinary Teaching Hospital in Pullman for care and treatment.

The main purpose of this study at Washington State University is to test the use of yttrium-90-RadioGel™ as a novel therapeutic agent against tumors that cannot be treated effectively by otherwise conventional means.

Why was yttrium-90-RadioGel™ selected for this study?  

Oncologists need an effective, high-dose injectable agent that can destroy neoplastic tissue without harming adjacent normal tissues and distal parts of the body. Surgeons can extract some tumors surgically, but in many cases, complete excision without surgical damage to the patient is not possible (such as where amputation may not be optional).  Cancers may also invade adjacent normal tissues, and surgery is not advised in cases where tumor resection may cause severe patient complications. Often chemotherapy will not provide tumor reduction without excessive toxicity, and external beam radiation may not be able to provide sufficiently high doses to adequately treat deeply seated tumors without negative effects on normal tissues. 

Yttrium-90 RadioGel™ may be indicated for tumors that can be injected during surgical intervention or by image-guided percutaneous injection in cases where no other standard therapies could provide better outcomes for the patient.  Direct placement within the tumor of a high-energy, short-range beta-particle emitter (yttrium-90) as a high radiation dose agent, however, provides an opportunity to destroy the tumor structure and its margins without harmful side effects to nearby tissues or other internal organs.

But experience using yttrium-90-RadioGel™ is limited.  Therefore, the principle objectives of the research at Washington State University are twofold: (1) to gain valuable physician experience with injection techniques (handling, mixing, needle placement, ultrasound support, radiation safety, and patient care), and (2) to show evidence of objective response (tumor cell destruction) without any of the negative side effects that are common in other cancer treatment modalities.

The study principal investigator is Dr. Darrell Fisher, a medical physicist with many years of practical experience designing and testing new radiopharmaceuticals as therapeutic agents against different types of cancer.  Fisher is Research Professor of Pharmacy at Washington State University and nuclear medicine physicist with Versant Medical Physics and Radiation Safety.  The lead clinical specialist is Dr. Janean Fidel, D.V.M. and Professor of Veterinary Medicine at Washington State University, with board certifications in both medical and radiation oncology.  

The Washington State University study is also a “dose-escalation” study so that safety and efficacy can be more completely demonstrated as the test infusions are increased to curative levels.  New therapeutic agents are usually introduced step-wise under carefully executed studies so that both efficacy and safety can be demonstrated to the Food and Drug Administration.  Dose escalation means that early treatments may be given at lower doses than will ultimately be used to achieve optimum therapeutic outcomes.  While the importance of achieving complete cures in cancer treatment is paramount, it is also essential to gain practical experience using the product successfully and to achieve broad physician acceptance of RadioGel™ as a new therapeutic modality of choice.   

Figure 1.  Radiation-related tumor necrosis and inflammation in a tumor section obtained from a cat treated for feline sarcoma with Y-90-RadioGel™ (photo courtesy Washington State University).

What have we learned from this study?

Thus far, two cats with vaccine-associated feline sarcoma have been treated by the study team at Washington State University.  Results of these treatment are summarized, as follows:

1. Valuable medical experience was gained by the clinical team
2. The team demonstrated successful injection techniques, guided by ultrasound, for distributing the Y-90-RadioGel™ throughout the tumor structure
3. The RadioGel™ carrier materials performed as expected before and after injection
4. The clinical team demonstrated successful radiation safety techniques without measurable radiation dose to any of the clinical staff
5. The cat patients recovered quickly from anesthesia without negative side-effects of treatment
6. Response of the tumor tissue to Y-90 radiation therapy was evaluated by pre-injection and post-injection CT scans, cell viability uptake markers, and by histological examination of excised tumor tissue; the study team confirmed an objective response with clear indications of tumor cell destruction associated with localized radiation delivery

This clinical research study will continue at higher overall radiation doses to tumors in subsequent cat subjects.  A key aspect of the research will be ability to uniformly distribute the Y-90-RadioGel™ evenly throughout the tumor.  Even at less-than-optimum starting doses, the researchers have observed massive therapy-related tumor necrosis (Figure 1) without demonstrable negative side effects elsewhere in the patient.  Research to date support interpretation in terms of a highly promising therapeutic index (a key ratio of dose to tumor relative to dose to any critical normal organ in the patient).  The implication of this index is tumor-destruction efficacy within the context of a comprehensive safety profile.

The therapeutic effects of localized beta radiation from yttrium-90 are well-established in the literature, and thus it has not been the purpose of this research to date to reprove known facts.  The more important aspects are practical experience leading to streamlined clinical use and increased physician acceptance for future applications in cancer treatment for both pets and humans.  Thus far, the results of this work indicate that the potential for Y-90-RadioGel™ appears highly promising from all perspectives.