Method for locating, differentiating, and removing neoplasms

• US 4,782,840 A
• Filed: 09/10/1986
• Issued: 11/08/1988
• Est. Priority Date: 03/02/1984
• Status: Expired due to Term

• Current Assignee: Neoprobe Corporation
• Original Assignee: Neoprobe Corporation
• Inventors: Thurston, Marlin O., Martin, Edward W. Jr.
• Primary Examiner(s): Cohen, Lee S.
• Assistant Examiner(s): Hanley, John C.
• Application Number:
  US06/905,880
• Time in Patent Office: 790 Days
• Field of Search: 128/654, 128/659, 128/653
• US Class Current: 600/431
• CPC Class Codes: A61B 10/00 Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis vaccination prophylaxis, vaccination therapy A61B17/20; Sex determination; Ovulation-period determination menstruation tables G06C3/00; Throat striking implements
• CPC Class Codes: A61B 2090/392 Radioactive markers

Abstract

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.

Claims

1. In 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 which comprises:

(a) administering to said animal an effective amount of a labelled antibody specific for neoplastic tissue and being labelled with a radioactive isotope exhibiting photon emissions of select energy levels;

(b) delaying said surgery for a time interval following said administering for permitting said labelled antibody to preferentially concentrate in any neoplastic tissue present in said animal and for the unbound labelled antibody in the blood pool to be cleared to a blood pool background level, so as to increase the ratio of photon emissions from neoplastic tissue to background photon emissions in said animal;

(c) after said delaying, surgically accessing the operative field of said animal;

(d) determining the background photon emission count for tissue within said operative filed which is to be examined for neoplastic tissue;

(e) manually positioning a hand-held probe within said operative field adjacent tissue suspected of being neoplastic, said probe configured for facile hand positioning and maneuvering within said operative field of said animal and 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, amplifier means having an input coupled with said radiation detector output pulses, and readout means responsive tos aid output pulses and actuable to an initial condition for commencing the provision of a perceptible indication of an inidica corresponding to the number of said output pulses received;

(f) determining from said perceptible indication the extent of tissue exhibiting a number of said output pulses having a value above said background output pulses for tissue within said operative field as determined in step (d); and

(g) surgically removing a sample of said tissue determined in step (f) for histological analysis of said sample.

2. The surgical procedure of claim 1 wherein said perceptible output comprises sound.

3. The surgical procedure of claim 1 wherein said antibody is selected from the group consisting of a whole polyclonal antibody, a whole monoclonal antibody, a fragment antibody, or mixtures thereof.

4. The surgical procedure of claim 1 wherein said isotope exhibits select energy levels of not above about 300 kev.

5. The surgical procedure of claim 1 wherein said surgery is delayed for a time period of at least about 7 days.

6. In 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 which comprises:

(a) administering to said animal an effective amount of a labelled antibody specific for neoplastic tissue and being labelled with a radioactive isotope exhibiting photon emissions of select energy levels;

(b) delaying said surgery for a time interval following said administering for permitting said labelled antibody to preferentially concentrate in any neoplastic tissue present in said animal and for the unbound labelled antibody in the blood pool to be cleared to a blood pool background level, so as to increase the ratio of photon emissions from neoplastic tissue to background photon emissions in said animal;

(c) after said delaying, surgically accessing the operative field of said animal;

(d) determining tissue within the operative field which is suspected of being neoplastic;

(e) surgically removing a sample of said tissue determined in step (d);

(f) manually positioning a hand-held probe adjacent said removed tissue suspected of being neoplastic, said probe 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, amplifier means having an input coupled with said radiation detector output and responsive to said discrete signals to provide corresponding amplified output pulses, and 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; and

(g) determining from said perceptible indication the extent of any tissue in said sample which exhibits a number of said output pulses having a value above background.

7. The surgical procedure of claim 6 wherein tissue determined in step (g) then is subjected to histological analysis.

8. The surgical procedure of claim 6 wherein for a sample which is determined to be neoplastic in step (g), tissue in said animal adjacent said sample is surgically removed.

9. The surgical procedure of claim 6 wherein said perceptible output is selected from the group consisting of sound, light, a chart, or combinations thereof.

10. The surgical procedure of claim 6 wherein said antibody is selected from the group consisting of a whole polyclonal antibody, a whole monoclonal antibody, a fragment antibody, or mixtures thereof.

11. The surgical procedure of claim 6 wherein said isotope exhibits select energy levels of not above about 300 kev.

12. The surgical procedure of claim 6 wherein said surgery is delayed for a time period of at least about 7 days.

13. In 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 which comprises:

(a) administering to said animal an effective amount of a labelled antibody specific for neoplastic tissue and being labelled with a radioactive isotope exhibiting photon emissions of select energy levels;

(b) delaying said surgery for a time interval following said administering for permitting said labelled antibody to preferentially concentrate in any neoplastic tissue present in said animal and for the unbound labelled antibody in the blood pool to be cleared to a blood pool background level, so as to increase the ratio of photon emissions from neoplastic tissue to background photon emissions in said animal;

(c) after said delaying, surgically accessing the operative field of said animal;

(d) determining the background photon emission count for tissue within said operative field which is to be examined for neoplastic tissue;

(e) manually positioning a hand-held probe within said operative field adjacent tissue suspected of being neoplastic, said probe configured for facile hand positioning and maneuvering within said operative field of said animal and 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, amplifier means having an input coupled with said radiation detector output and responsive to said discrete signals to provide corresponding amplified output pulses and 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;

(f) determining from said perceptible indication the extent of tissue exhibiting a number of said output pulses having a value above said background output pulses for tissue within said operative field as determined in step (d);

(g) surgically removing said tissue determined in step (f);

(h) manually positioning said probe adjacent said tissue surrounding said surgically removed tissue to determine from said perceptible indication whether any of said surrounding tissue exhibits a number of output pulses having a value above said tissue background output pulses;

(i) surgically removing any tissue determined in step (h); and

(j) repeating steps (h) and (i) until no more tissue is determined.

14. The surgical procedure of claim 13 wherein said perceptible output comprises sound.

15. The surgical procedure of claim 13 wherein said antibody is selected from the group consisting of a whole polyclonal antibody, a whole monoclonal antibody, a fragment antibody, or mixtures thereof.

16. The surgical procedure of claim 13 wherein said isotope exhibits select energy levels of not above about 300 kev.

17. The surgical procedure of claim 16 wherein said select energy levels are not above about 150 kev.

18. The surgical procedure of claim 13 wherein said isotope is selected from the group consisting of Iodine 131, Iodine 125, Indium 111, Selenium 75, Cobalt 57, and mixtures thereof.

19. The surgical procedure of claim 13 wherein said surgery is delayed for a time period of at least about 7 days.

20. The surgical procedure of claim 19 wherein said surgery is delayed for a time interval ranging from about 7 to 21 days.