The Ohio State University

Neoprobe Corporation

Phylatron Ltd.

Edward W Martin

Charles L Hitchcock

Heather C Allen

James Coe

Thomas J Magliery

Alper Yilmaz

Nicholas E Long

Brandon J Sullivan

E David Alten

Enver Ozer

Stephen P Povoski

Ronald Xu

Emilio Barbera-Guillem

Marlin O Thurston

Eugene A Woltering

Pierre L Triozzi

Brian J Czerniecki

Julian A Kim

Thomas M O'Dorisio

M Sue O'Dorisio

Disclosed are systems and methods utilizing an infrared probe and discriminating software to rapidly discriminate abnormal tissue processes from normal tissue during surgery, physical examination of in-situ lesions, and in the assessment of biopsy and resected tissue specimens. Examples demonstrate discrimination of cancerous from noncancerous tissues. The discriminating software, i.e. the metrics, algorithms, calibrant spectra, and decision equations, allows tissue to be identified as abnormal or normal using a minimum of infrared (IR) wavelengths in order to be measured rapidly. The probe records IR metrics approximately 1000 times faster than current commercial instruments, i.e. on a timescale fast enough for clinical use. The probe uses a tunable mid-infrared laser with a small set of selected wavelengths that are optimized for detecting the chemical and molecular signatures of tissue specific lesions to include, but not limited to, cancer, preneoplasia, intracellular accumulations (e.g. steatosis), inflammation, and wound healing.

Discrimination of tissues using a fast infrared probe

System and method for the discrimination of tissues using a fast infrared cancer probe

Systems and methods utilize an infrared probe and discriminating software to rapidly discriminate normal tissue processes from normal tissue during surgery, physical examination of in-situ lesions, and in the assessment of biopsy and resected tissue specimens. Examples demonstrate discrimination of cancerous from noncancerous tissues. The discriminating software, i.e. the metrics, algorithms, calibrant spectra, and decision equations, allows tissue to be identified as abnormal or normal using a minimum of infrared (IR) wavelengths in order to be measured rapidly. The probe records IR metrics approximately 1000 times faster than current commercial instruments, i.e. on a timescale fast enough for clinical use. The probe uses a tunable mid-infrared laser with a small set of selected wavelengths that are optimized for detecting the chemical and molecular signatures of tissue specific lesions to include, but not limited to, cancer, preneoplasia, intracellular accumulations (e.g. steatosis), inflammation, and wound healing.

Systems and methods are described for performing navigation-assisted medical procedures such as biopsies, surgeries and pathology procedures by obtaining location information of an item of interest located within at least a portion of a subject; sensing position information of a moveable device; determining a relative position of the moveable device to the item of interest using the location information of the item of interest and the position information of the moveable device; and providing feedback based on the relative position of the moveable device to the item of interest that can be used to change the relative position of the moveable device to the item of interest.

Methods and systems for performing navigation-assisted medical procedures

Disclosed herein are methods and compositions related to single chain antibody fragments which specifically bind sialyl-Tn epitope of tumor-associated glycoprotein 72 (TAG-72).

Methods and compositions related to single chain antibody fragments that bind to tumor-associated glycoprotein 72 (TAG-72)

A method is provided for immune corrective surgical removal of lymphoid tissues containing shed tumor antigen in an individual. A detector molecule, with binding specificity for shed tumor antigen, is administered to an individual, and detected in the individual is the presence of lymphoid tissue which contains shed tumor antigen, as detected by the signal emitted by the detector molecule bound to shed tumor antigen. The lymphoid tissue, detected as containing shed tumor antigen, may then be surgically removed, thereby removing B cells, shed tumor antigen, and follicular dendritic cells involved in a pro-tumor immune response that are contained in the removed lymphoid tissue.

Method for detecting and surgically removing lymphoid tissue involved in tumor progression

The present invention is directed to a method for reliably determining lymph nodes enriched in tumor reactive cells, e.g., CD4+tumor-specific lymphocytes. This method includes the steps of administering to a patient an effective amount of a radiolabeled locator which specifically binds a marker produced by or associated with neoplastic tissue. Time is permitted to elapse following the administration for the radiolabeled locator to preferentially concentrate in any neoplastic tissue and for unbound radiolabeled locator to be cleared, so as to increase the ratio of photon emissions from neoplastic tissue to background photon emissions in the patient. After the time has elapsed, the patient is accessed with a radiation detection probe for determining lymph node sites exhibiting accretion of the radiolabeled locator by detecting with the probe elevated levels of radiation at the lymph node sites. The lymph node sites exhibiting such elevated levels of radiation are removed and subjected to gross visual analysis, though such sites alternatively may be subjected to histological analysis. Those determined and removed lymph nodes that also are determined to be tumor-free by gross observation or free of gross metastatic disease are selected and cultured to proliferate tumor reactive cells. The selected lymph nodes are subjected to mitogenic stimulation. The lymph nodes are cultured in the presence of Interleukin-2, anti-CD.sub.3 monoclonal antibody, and neoplastic tissue which may be autologous or allogeneic tumor. The tumor reactive cells, proliferated can be used with adoptive immunotherapy regimens for mitigating the progression of tumor.

Determination of lymph nodes enriched in tumor reactive cells their

Broadly, the present invention is directed to a method for the detection and differentiation of neoplastic tissue in a patient suspected of having neoplastic tissue. The method includes the administration of a radiolabeled somatostatin congener to the patient and accessing the patient with a radiation detection probe for determining tissue exhibiting elevated levels of radiation, viz., neoplastic tissue. However, before subjecting the patient to such administration, an initial determination preferably is made as to whether the radiolabeled somatostatin congener will bind to the tumor site, i.e., whether somatostatin receptors are associated with the neoplastic tissue. This is conveniently done with a wide variety of endocrine tumors, which release peptides or hormones, referred to as 'biochemical markers. ' In order to make this determination, initially a biochemical marker-inhibiting dose of unlabeled somatostatin congener is administered to the patient. The biochemical marker associated with the neoplastic tissue then is monitored to determine whether the administered somatostatin congener reduces the presence of the marker in the patient. If the monitored presence of the marker was reduced, then the surgeon can be confident that the neoplastic tissue or tumor contains receptors to which the somatostatin will bind. Thus, the administration of radiolabeled somatostatin congener is appropriate for such patient. If the biochemical marker associated with the neoplastic tissue is not appropriately reduced following the administration of the unlabeled somatostatin congener, then the neoplastic tissue may not be determinable by the use of radiolabeled somatostatin congener and alternative modalities of treatment should be considered, such as the use of radiolabeled antibodies as proposed in U.S. Pat. No. 4,782,840. If the tumor is of a type that does not release a biochemical marker, the presence of somatostatin receptors can be confirmed by other means, such as pathology, immunohistochemistry, radioreceptor assay, or such other means as will be apparent to those skilled in the art.

Application of peptide/cell receptor kinetics utilizing radiolabeled

Broadly, the present invention is directed to a method for reliably staging adenocarcinomas typified by colorectal cancer in patients who are undergoing surgery therefor. The method includes the administration of a radiolabeled tumor-associated glycoprotein (TAG) antibody (or other equivalent locator) to the cancer patient prior to surgical accession of the patient. Desirably, the present method includes surgical accession with a radiation detection probe for determining tissue exhibiting elevated levels of radiation. The preferred radiolabel is .sup.125 I, which is used to label an antibody specific to a high molecular weight glycoprotein called TAG-72. The preferred antibody is CC49, a murine monoclonal antibody of the IgG.sub.1 subclass. With radiolabeled monoclonal antibody CC49, it preferably is administered to the patient approximately 21 days (.+-.4 days) prior to surgery. Following surgical excision of all such tissue which is amenable to excision, the probe is again used to identify any remaining neoplastic tissue or tissue deposits, which may or may not be subjected to further excision attempts. After all possible excision of neoplastic tissue has occurred, final counts are taken with the probe to identify residual tissue deposits not excised. The number and location of the remaining tissue deposits form the basis of the biostaging system disclosed herein.

Biostaging of adenocarcinomas utilizing radiolabeled tumor-associated

The present invention is addressed to a method for the improved localization, differentiation, and removal of neoplastic tissue in animals. In particular, one aspect of the present invention involves a surgical procedure wherein an animal suspected of containing neoplastic tissue is surgically accessed and the tissue therein examined visually and by palpation for evidence of neoplastic tissue. The improved methodology commences with the administering to the animal of an effective amount of a labelled antibody specific for neoplastic tissue and labelled with a radioactive isotope exhibiting specific photon emissions of energy levels. Next, and importantly, the surgial procedure is delayed for a time interval following said administering for permitting the labelled antibody to preferentially concentrate in any neoplastic tissue present in the animal so as to increase the ratio of photon emissions from neoplastic tissue to background photon emissions in said animal. Thereafter, an operative field of the animal is surgically accessed and tissue within the operative field to be examined for neoplastic tissue has the background photon emission count determined. Once the background photon emission account for tissue within the operative field has been determined, a handheld probe is manually positioned within the operative field adjacent tissue suspected of being neoplastic. The probe is configured for fascile hand positioning and maneuvering within the operative field of the animal. The probe is characterized by having a collimatable radiation detector having a selective photon entrance and having an output deriving discrete signals responsive to photon emissions when said entrance is positioned immediately adjacent thereto. The probe further comprises amplifier means having an input coupled with said radiation detector output and responsive to said discrete signals to provide corresponding amplified output pulses. Finally, the probe comprises readout means responsive to said output pulses and actuable to an initial condition for commencing the provision of a perceptible indication of an indicia corresponding to the number of said output pulses received. From the perceptible indication, the extent of tissue exhibiting a number of output pulses having a value above background output pulses is determined and such determined tissue removed surgically. Thereafter, the probe is manually positioned adjacent tissue surrounding the surgically removed tissue to determined from said perceptible indication whether any of said surrounding tissue still exhibits a number of output pulses having a value above said background output pulses. Any adjacent tissue surrounding the initial surgically removed tissue which does exhibit an increased number of output pulses is surgically removed additonally. Thereafter, the margins again are examined with the probe in order to ensure that all tissue exhibiting a number of output pulses having a value above the background output pulses has been removed.

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Delaware, OH, United States of America

Edward W Martin