Radioimmunoscintigraphy with Tc-99m-labelled SM3 in differentiating malignant from benign adnexal masses.

OBJECTIVE: Ultrasound scanning, serum CA125 and menopausal status have previously been combined in a risk of malignancy index for the differential diagnosis of adnexal masses. Although this approach has greater accuracy than either individual tests or clinical assessment, it has a significant false positive and false negative rate. Efforts have been directed at refining differential diagnosis and this study assessed the role of radioimmunoscintigraphy using the stripped mucin 3 (SM3) antibody that has a 17-fold greater uptake in malignant than benign ovarian tumours in vitro. DESIGN: Prospective study of patients with a pelvic mass using radioimmunoscintigraphy. SETTING: Department of Nuclear Medicine of St Bartholomew's Hospital in collaboration with Cancer Network. POPULATION: A total of 93 patients with pelvic masses were recruited for this study of which 32 had ovarian cancer and 61 had benign lesions. METHODS: Radioimmunoscintigraphy was performed with Tc-99m-labelled SM3 (600 MBq), anterior and posterior pelvis imaged at 10 minutes and at 4 and 24 hours and evaluated with change detection analysis and probability mapping. MAIN OUTCOME MEASURES: Sensitivity and specificity of radioimmunoscintigraphy for ovarian cancer. RESULTS: Radioimmunoscintigraphy had a sensitivity for ovarian cancer of 84% (27 true positive and 5 false negatives) and a specificity of 87% (53 true negatives and 8 false positives) giving a negative predictive value of 91%. CONCLUSION: These results suggest that radioimmunoscintigraphy could be used to reduce the number of false positive findings in a strategy to refine differential diagnosis of the pelvic mass.

Axillary node status in breast cancer patients prior to surgery by imaging with Tc-99m humanised anti-PEM monoclonal antibody, hHMFG1.

In early breast cancer axillary nodes are usually impalpable and over 50% of such patients may have an axillary clearance when no nodes are involved. This work identifies axillary node status by imaging with a Tc-99m radiolabelled anti-Polymorphic Epithelial Mucin, humanised monoclonal antibody (human milk fat globule 1), prior to surgery in 30 patients. Change detection analysis of image data with probability mapping is undertaken. A specificity of 93% and positive predictive value of 92% (both 100% if a second cancer in the axilla with negative nodes is considered) were found. A strategy for combining negative imaging with the sentinel node procedure is presented.

Efficacy of immunoscintigraphy for detection of lymph node metastases.

The size of a lymph node is not in principle a limitation for the detection of cancer by Nuclear Medicine techniques. A radioactive pinhead is detectable if it has enough radioactivity on it. The approach of Nuclear Medicine to the demonstration of impalpable lymph nodes or to those lymph nodes detected by radiological techniques that are under 1 cm as to whether or not they contain cancer, is to increase the activity attached to cancer cells in such a lymph node as much as possible and to use sophisticated image analysis techniques to distinguish such uptake from its environment. This may be undertaken using a non specific technique such as F-18 Deoxyglucose and Positron Emission Tomography which is highly sensitive and which has been successful. The alternative approach is to use a highly specific and sensitive agent, such as a radio-labelled peptide or a radio-labelled monoclonal antibody together with image analysis. This paper describes these approaches and in particular the use of Tc-99m SM3 monoclonal antibody in the detection of impalpable axillary nodes in patients with breast cancer before surgery, using a change detection analysis providing a probability map of the significance of uptake of this radiopharmaceutical. It is a robust approach, providing the patient and the surgeon with information as to the likely need for extensive axillary surgery well prior to operation. A negative study should be followed by a sentinel node evaluation at surgery.

Imaging with prostate-specific membrane antigen (PSMA) in prostate cancer.

Radioimmunoscintigraphy using a radio-labelled antibody to prostate-specific membrane antigen (PSMA) has growing applications as a means of tissue-specific imaging based on functional characteristics and complements traditional staging investigations. Clinical applications in men with carcinoma of the prostate are being refined, and this study reports outcomes with this technique in our practice. Prostatic immunoscintigraphy scans were performed with In-111 CYT 356 in 49 men with carcinoma of the prostate, obtaining sequential images in two and three dimensions at 10 min, 24 and 48 h. Of the 49 men, 36 had clinically localized cancer, 10 had recurrent disease after radical radiotherapy or radical prostatectomy and three had rising PSA after primary endocrine treatment. Scan findings are discussed in the context of clinical management. Of the 36 men with clinically localized cancer, seven had increased uptake in regional and distant lymph nodes. Of these seven, three were treated with hormone manipulation, two by radical prostatectomy and two by radical radiotherapy. Among 10 patients who had recurrence after radical treatment of the primary tumour, scans showed local recurrence alone in four, and six had regional or distant metastases. Three patients treated with primary hormone manipulation had scans for rising PSA, and of these one had a positive regional node and two had distant soft tissue and bone metastases. In conclusion, prostatic radio-immunoscintigraphy scans highlight tissues involved by prostate cancer, including the prostate, lymph nodes, soft tissues and bone metastases as well as pelvic recurrence. Results may contribute to the clinical management of individual patients, although histological confirmation may be appropriate when considering alternative treatment. Prostate Cancer and Prostatic Diseases (2000) 3, 47-52

Effect of radioimmunoscintigraphy on the management of recurrent colorectal cancer.

BACKGROUND: Radioimmunoscintigraphy (RIS) is being used increasingly as a new investigation in the diagnosis of recurrent colorectal cancer. This study assessed the efficacy of 99mTc-radiolabelled PR1A3 scanning in a cohort of patients with possible recurrent colorectal cancer and the effects of scan interpretation on subsequent clinical management. METHODS: The scans and case notes of patients scanned over a 3-year period were reviewed. RESULTS: Forty-seven scans in 40 patients were available for analysis. In 39 instances in which scan interpretation could be verified accurately, sensitivity for recurrent colorectal cancer was 22 of 23 (96 per cent), specificity for recurrent colorectal cancer was eight of 16 (50 per cent), positive predictive value for recurrence was 22 of 30 (73 per cent) and negative predictive value for recurrence was eight of nine (89 per cent). In 16 of the 40 patients, scan interpretation strengthened a management decision or altered management. This was beneficial to ten patients and possibly detrimental to six. CONCLUSION: This study demonstrated that RIS is sensitive in the detection of recurrent colorectal cancer and benefited the patient in one-quarter of cases. For the majority of patients, accurate detection of recurrent disease cannot be followed by curative therapy, but there is an important subgroup of patients in whom RIS alters management beneficially. However, a randomized prospective study is needed to confirm this.

99mTc-labelled SM3 in the preoperative evaluation of axillary lymph nodes and primary breast cancer with change detection statistical processing as an aid to tumour detection.

The extent of primary surgery for breast cancer could be tailored to the patient if previous information on the presence or absence of lymph node involvement could be reliably determined. Prospective radioimmunoscintigraphy in 29 patients with primary breast cancer that was found on screening has been undertaken with 555 MBq (15 mCi) 99mTc SM3, an Imperial Cancer Research Fund (ICRF) murine monoclonal antibody, 0.5 mg with images at 10 min and 22 h, and analysis using a change detection algorithm. Sites of significant change between the early and later images were displayed as a map of probabilities. Image-positive and -negative axillary lymph nodes were compared by histology in the 28 evaluable patients. The correct identification of the presence or absence of node involvement, even if impalpable, has been shown in 24 out of 28 patients (29 lymph node groups). Sensitivity was 90% (nine out of ten), specificity 84% (16 out of 19) and accuracy 86%. These results encourage further assessment of this technique.

Imaging prostate cancer with technetium-99m-7E11-C5.3 (CYT-351).

UNLABELLED: To evaluate the performance of the 99mTc-labeled monoclonal antibody CYT-351 in visualizing prostate cancer, radioimmunoscintigraphy (RIS) was performed in 35 patients. METHODS: Antibody (0.5 mg) labeled with 600 MBq 99mTc was injected intravenously after obtaining informed consent. Planar and SPECT imaging was performed at 10 min and 6-8 and 22-24 hr postinjection. The scans were evaluated for visualization of the primary focus or local recurrence, extraprostatic invasion, lymph node involvement and uptake in bone and soft tissue metastases. RESULTS: Thirty-six studies in 35 patients were performed. In 13/14 evaluable studies with clinically localized prostate cancer, RIS had a true-positive rate of 92% (12/13). In eight patients with previous incidental carcinoma detected during transurethral resection undertaken for clinically benign disease, there were 86% true-positive results (6/7) and one true-negative result, which were confirmed by systematic needle biopsies. In six patients with evidence of local recurrence after a previous radical prostatectomy, the true-positive rate was 100% (6/6), which was confirmed by raised or rising prostate-specific antigen levels (PSA) and/or by biopsy. In the eight patients with known metastases, the disease was visualized in 4/4 with progression but not in the 3/3 with regression; one patient demonstrated regressing disease as determined by PSA levels. The overall accuracy was 92%. CONCLUSION: RIS with 99mTc CYT-351 is capable of providing good quality images and yielding clinically useful information safely. It has a potentially important clinical role for patients with rising PSA levels but negative images by conventional modalities.

Prostatic radioimmunoscintigraphy: preliminary results using technetium-labelled monoclonal antibody, CYT-351.

OBJECTIVE: To investigate the clinical application of a new technique for imaging prostatic malignancy using planar imaging and single-photon emission tomography (SPET) with technetium-99m-labelled antibody to a prostatic cell surface membrane antigen. PATIENTS AND METHODS: Prostatic malignancy was imaged by radioimmunoscintigraphy (RIS) using a 99mTc-labelled monoclonal antibody, CYT-351, raised against a newly identified membrane antigen present in normal and malignant prostatic tissues. The protocol involved taking serial images and assessing the changes in activity, as the uptake of specific antibody increased with time and non-specific uptake decreased. Data from planar images were collected at 10 min, 6 and 24 h after injection with antibody, and by SPET at 6 and 24 h using a Siemens Orbiter Large Field of View gamma camera. Twenty-two RIS scans were evaluated, which included six patients with clinically localized disease, six patients with previous incidental carcinoma at prostatectomy for apparently benign disease, four patients with evidence of local recurrence after radical prostatectomy and six patients with metastatic disease. RESULTS: Primary tumours and secondary lymphatic and bone metastases were demonstrated. Only one minor side-effect was experienced. CONCLUSION: This RIS technique was capable of imaging primary prostatic malignancy and metastatic disease in lymph nodes and bone. Its clinical application remains to be defined, but potentially it provides a new means for tumour staging based upon tissue characterization. It may be particularly useful before radical prostatectomy and it is capable of imaging local recurrence following radical treatment of localized disease. Future applications include monitoring the progression of disease and the response to treatment.

Immunoscintigraphy: Importance for researchers and patients.

One of the subtle differences between the cancer cell surface and the normal cell is exploited by immunoscintigraphy. The clinical role and some technical aspects of imaging cancer with radiolabelled antibodies are reviewed. 99mTc is the best radiolabel for immunoscintigraphy. Specificity is added to the general sensitivity of nuclear medicine techniques by this approach to imaging cancer.

Breast cancer 99mTc SM3 radioimmunoscintigraphy.

99mTc SM3 radioimmunoscintigraphy is combined with kinetic analysis and probability mapping using a change detection algorithm to investigate axillary node involvement before primary surgery in patients with breast cancer. Whereas planar imaging was unsuccessful, axillary node involvement was correctly determined in 11 out of 13 patients 6 out of 7 true negatives and 5 out of 6 true positives down to 0.35 grams. A prospective study is underway.

Peroperative radioimmunodetection of ovarian carcinoma using a hand-held gamma detection probe.

Radioimmunoscintigraphy (RIS) can be used in the preoperative localisation of ovarian carcinoma to demonstrate uptake of radiolabelled monoclonal antibodies into neoplastic tissue. The tissue uptake of radiotracer was evaluated at laparotomy in 16 patients with suspected ovarian cancer who had preoperative RIS using technetium-99m-labelled monoclonal antibodies SM3 and H17E2. A gamma detection probe (gamma DP) was used to measure uptake in possible tumour deposits at operation and also the uptake in tissues resected for histology. The percentage uptake of the initial injected dose of radiotracer was also measured in resected tissues. Activity was found to be significantly higher in malignant than in non-neoplastic tissue by all three methods of evaluation. The gamma DP used peroperatively yielded a 82% sensitivity with a 72% specificity for an uptake ratio of 1.5:1. When tissue was examined immediately after resection, for a 100% specificity the sensitivity was 64%. In vitro measurements of monoclonal antibody uptake by tissue similarly gave a 65% sensitivity with a 100% specificity. Peroperative and immediate post-operative measurements of tissue radioactivity can be performed quickly and conveniently, and in some cases may be of benefit in the localisation of tumour at laparotomy and in providing extra information when tissue is examined by frozen section.

Radioimmunoscintigraphy with technetium-99m labelled monoclonal antibody, 1A3, in colorectal cancer.

This study of radioimmunoscintigraphy (RIS) was primarily undertaken to determine how the imaging results related to surgical findings. Technetium-99m radiolabelled 1A3, a monoclonal antibody against a columnar cell surface antigen, was used. No adverse effects or thyroid uptake was observed in 127 studies. The 85 primary colorectal cancers were all image positive. In the assessment of recurrent tumour in the abdomen or pelvis, the accuracy was 33/35 (94%), including true-positive findings in some whose serum carcinoembryonic antigen was normal. There was a positive predictive value for abdominal or pelvic recurrence of 92% and a negative predictive value of 100%, at a prevalence of 66%. In those patients whose liver was able to be evaluated, the accuracy was 72/79 (91%). There was a positive predictive value for liver metastases of 88% and a negative predictive value of 93%, at a prevalence of 32%. The simple procedure for labelling antibody with 99mTc and its ready availability allow a completed report to be given within 24 h of the request.

Radioimmunoscintigraphy with technetium-99m-labelled monoclonal antibody, SM3, in gynaecological cancer.

Radioimmunoscintigraphy (RIS) with technetium-99m labelled SM3, a monoclonal antibody reacting with a polymorphic epithelial mucin glycoprotein core antigen, is evaluated. No adverse effects or thyroid uptake were observed. Studies in 45 patients (one twice) had a sensitivity for gynaecological malignancy of 100% (35/35) and a specificity of 73% (8/11), giving an overall accuracy of 93% (43/46). These results have led to the routine adoption of 99mTc RIS in the management of patients suspected of or having primary or recurrent gynaecological cancer.

Disturbed gastric and small bowel transit in severe idiopathic constipation.

Many patients with severe idiopathic constipation complain of upper gastrointestinal symptoms, and these often persist after subtotal colectomy. To determine if there is a disturbance of upper gastrointestinal motility in this condition, we have studied gastric emptying for solids (111In-containing pancake) and liquids (99mTc-containing orange juice) for a longer period after a meal (6 hr) than in previously reported gastric emptying studies. Small bowel transit for solids was also measured. All patients had emptied their colon the day before the study. Twelve women (mean age 36 years) with a bowel frequency of less than once per week, proven slow intestinal transit, and a normal diameter colon were studied. Twelve healthy controls (eight female and four male, mean age 33) were also studied. As a group the constipated patients demonstrated no statistically significant delay in emptying during the first 3 hr, although the emptying rate for three of 12 individuals fell outside the normal range. However, at 6 hr after ingestion of the meal, six of 10 patients had residual gastric contents greater than normal--up to 48% solid residue (median: 11% for patients and 0% for controls, P < 0.01) and 40% of liquid (median 9% vs 0%, P < 0.01). Three of four patients with upper gastrointestinal symptoms 6 hr after the meal had gastric retention of solids markedly outside the normal range (48%, 32%, and 16%; normal < 4%). Small bowel transit time was assessed as the time for the solid phase to pass from the duodenum to the cecum; the constipated patients demonstrated delayed transit (median: 75 vs 55 min, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Duodeno-gastric reflux and gastric adenomas: a scintigraphic study in patients with familial adenomatous polyposis.

To test whether the presence of gastric adenomas (dysplasia) was associated with gastric reflux of duodenal contents, six patients with familial adenomatous polyposis (FAP) who had gastric adenomas and nine matched FAP patients without gastric adenomas underwent scintigraphic duodeno-gastric reflux scanning. Reflux was graded 0-6, where 0 = no reflux, 1 = intermittent reflux into antrum only, 2 = prolonged reflux into antrum only, 3 = intermittent reflux into body, 4 = prolonged reflux into body, 5 = intermittent reflux into body and fundus, and 6 = prolonged reflux into body and fundus. FAP patients with gastric adenomas had more severe reflux (median 6, range 4-6) than did controls (median 3, range 0-6; P = 0.009, Mann-Whitney U test). These results are consistent with a role for bile in the development of gastric adenomatous polyps and suggest that bile is involved in the dysplasia-carcinoma sequence.