Probe maker builds own MoAb agent

Gamma cameras aren't the only nuclear detectors that will takeadvantage of targeted monoclonal antibody nuclear tracer technology.Nonimaging probes, such as those manufactured by Neoprobe andCare Wise Medical Products (SCAN 9/26/90 and 12/04/91), use monoclonalagents to help guide the hands of oncological surgeons.

Neoprobe, however, will not use Cytogen's OncoScint agent,the first monoclonal imaging agent approved by the Food and DrugAdministration (SCAN 1/27/93). The Columbus, OH, firm is developingits own monoclonal antibody agent under license for use with itsradioimmunoguided surgery (RIGS) tumor detection system.

The monoclonal antibody used by RIGS is CC49, developed atthe National Institutes of Health. NIH licensed CC49 to Dow Chemical,which in turn sublicensed it to Neoprobe. The antibody is labeledwith iodine-125.

Neoprobe switched to CC49 after initially working with B72.3,the antibody used in Cytogen's OncoScint. The move to a new antibodydelayed development of RIGS by at least a year, according to Neoprobechairman and CEO John L. Ridihalgh, but the company had foundCC49 to be more effective than the other antibody.

"We were in a phase three trial with B72.3," Ridihalghsaid. "We started working on (CC49) and we found so muchmore cancer that we made the agonizing decision to drop B72.3."

The main component of Neoprobe's system is a gamma-ray detectingdevice called the Neoprobe 1000. This device consists of a probeabout the size of a small flashlight and a bread box-sized controlunit. Although Neoprobe 1000 has FDA 510(k) clearance, the companymust also gain FDA approval for the monoclonal component beforethe entire RIGS system can be marketed.

Neoprobe's monoclonal antibody is about to begin phase threetrials for colorectal cancer and has started phase two trialsfor ovarian cancer.

RIGS exemplifies the blend of therapy and diagnosis inherentin monoclonals. During RIGS-guided surgery, a patient is injectedwith radiolabeled monoclonal antibodies, which seek and bind tocancerous tissue. When a surgeon applies the probe to tissue believedto be cancerous, the control unit emits an audible signal if anyradioactivity is detected. The surgeon is thus able to removecancers that might have been missed if he or she were relyingon sight and touch to find tumors, Ridihalgh told SCAN.

"If the instrument tells surgeons there's more cancer,they'll keep going after it," he said. "If the probetells them there's nothing there, they'll go about their regularoperation with more confidence that they've done everything theycan to find the extent of the disease."

NEOPROBE COMPLETED AN INITIAL PUBLIC OFFERING in November thatraised $10 million to help the firm bring RIGS to market. Thecompany is traded on the NASDAQ exchange under the symbol NEOP.

Neoprobe 1000 will cost about $35,000. The company will generateongoing revenue through sales of the monoclonal antibodies usedby the device. Neoprobe is searching for a marketing partner forthe technology and is in discussions with surgical device vendors.

The company expects that the RIGS system will be used in conjunctionwith existing imaging technologies for cancer detection. Neoprobe1000 is more sensitive than standard external gamma cameras becauseof the probe's proximity to the tissue being examined, accordingto Ridihalgh. It can detect lymph nodes as small as 2 to 3 mmin diameter, he said.

But performing surgery on a patient for screening purposeshas obvious drawbacks. As a result, surgeons using RIGS will continueto rely on modalities such as CT and conventional nuclear medicineto identify the general location and extent of disease beforesurgery begins.

Neoprobe 1000's applications are not limited to colorectaland ovarian cancer, according to the company. The RIGS systemcould be used to detect all solid tumors that are surgically treatableand the company intends to expand its applications to other typesof cancer by developing the appropriate monoclonal antibodies.

Neoprobe also intends to market a beta-ray detecting probefor endoscopic and laparoscopic treatment of tumors. The technologywas developed by researchers at the University of California atLos Angeles, and Neoprobe signed a licensing agreement with theuniversity last month. The beta-ray probe is expected to be mosteffective for tumors near surface tissue, according to the company.

Will RIGS and similar probe systems be oncological surgery'smagic wand? Only time will tell, but surgeons participating inclinical studies with the Neoprobe device are finding 30% morecancer than without it, Ridihalgh said.

"Surgeons have had their hands and eyes as their diagnosticequipment during surgery for 100 years or more, and there reallyaren't any more significant advances to help them," Ridihalghsaid. "We think that surgeons can do a better job when they'vefound instruments that will help them find cancer."

BRIEFLY NOTED:

• Bristol-Myers Squibb has acquired marketing and manufacturingrights to a gastrointestinal ultrasound contrast agent in phasethree clinical trials. The product, SonoRx, is the first oralultrasound contrast agent, according to the company.

BMS acquired rights to the agent in December from ImaRx ofTucson, AZ, a BMS spokesperson said. Details of the agreementwill be released in March in conjunction with the American Instituteof Ultrasound in Medicine meeting in Hawaii.