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Human melanoma proteoglycan (HMP), a melanoma-associated antigen, is expressed in both human melanomas and gliomas. We used HMP-specific monoclonal antibody (mAb) VT68.2 to investigate whether murine GL261 cerebral gliomas express the HMP homologue AN2 and to determine whether AN2 could be targeted for selective delivery of radiation in vivo. HMP-specific mAb VT68.2 stained murine GL261 glioma cells grown in culture and intracerebrally in syngeneic C57BL/6 mice. Positron emission tomography with radiolabeled mAb VT68.2 showed high-contrast, positive images of gliomas against a negative background. At 96 h after injection, glioma uptake of radiolabeled mAb VT68.2 was 10 times greater than that of the isotype control mAb and 20 times greater than that detected in normal cerebral tissue. Our results show murine GL261 cerebral gliomas express AN2 and HMP-specific mAb VT68.2 accumulates selectively and specifically at high concentration and is retained within murine cerebral gliomas. Thus, HMP is a potential target for antibody-mediated selective delivery of radiation to cerebral gliomas in vivo.

Clinical immunolocalization has been attempted by others with an anti-Thomsen-Friedenreich antigen (TF-Ag) mAb that bound both alpha- and beta-linked TF-Ag. In this report, 124 I-labeled mAb JAA-F11 specific for alpha-linked TF-Ag showed higher tumor specificity in in vivo micro-positron emission tomography (micro-PET) of the mouse mammary adenocarcinoma line, 4T1, showing no preferential uptake by the kidney. Labeled product remained localized in the tumor for at least 20 days. Glycan array analysis showed structural specificity of the antibody.

BACKGROUND An adjunctive noninvasive test that is predictable and highly specific for breast carcinoma would complement the high false-positive rate of mammography in certain patients. METHODS This prospective, multicenter study evaluated the accuracy, safety, and immunogenicity of carcinoembryonic antigen (CEA) antibody imaging in women with known or suspected breast carcinoma. Scintigraphic breast images were obtained approximately 3–8 hours after the administration of technetium 99m (99Tc) labeled anti-CEA Fab′ and correlated with histopathology. RESULTS The 99Tc labeled anti-CEA Fab′ detected tumor CEA expression in 46 of 49 women (94%) initially entered with known primary breast carcinoma regardless of histology or serum CEA levels. In women scheduled for biopsy confirmation of mammographic and physical examination findings, 104 99Tc labeled anti-CEA Fab′ studies had a sensitivity of 61% (17 of 28 cases) and a specificity of 91% (69 of 76 cases). In total, 99Tc labeled anti-CEA Fab′ detected 52 of 62 invasive ductal carcinomas, 5 of 5 invasive lobular carcinomas, and 3 of 6 noninvasive tumors (2 ductal carcinomas in situ and 1 intracystic papillary carcinoma). Tumor size significantly affected sensitivity (P = 0.041), with 11 of 14 missed lesions ≤ T1, and proliferative histology significantly affected specificity (P = 0.012), with 5 of 7 false-positive tumors being premalignant. In 50 breast carcinoma patients, 99Tc labeled anti-CEA Fab′ also demonstrated axillary lymph node involvement regardless of serum CEA levels, with a sensitivity of 80% when more than three lymph nodes were positive. No immune response or other meaningful side effects occurred. CONCLUSIONS 99Tc labeled anti-CEA Fab′ had high specificity and positive predictive values for breast carcinoma and the majority of false-positive studies were associated with an increased risk of malignancy. Improved imaging techniques, including dedicated gamma cameras for breast and axillary lymph node imaging, will likely improve the test's sensitivity for smaller lesions. Cancer 2000;89:104–15. © 2000 American Cancer Society.

To evaluate the diagnostic usefulness of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in patients with primary colorectal carcinomas.Forty-eight patients with biopsy-proved (n = 44) or high clinical suspicion for (n = 4) colorectal cancer underwent whole-body PET after intravenous administration of 10 mCi (370 MBq) of FDG. FDG PET results were correlated with computed tomographic (CT), surgical, and histopathologic findings.PET depicted all known intraluminal carcinomas in 37 patients (including two in situ carcinomas) (sensitivity, 100%), but findings were false-positive in four of seven patients without cancer (three with inflammatory bowel conditions, one who had undergone polypectomy). Specificity was 43% (three of seven patients); positive predictive value, 90% (37 of 41 patients); and negative predictive value, 100% (three of three patients). No FDG accumulation was noted in 35 hyperplastic polyps. FDG PET depicted lymph node metastases in four of 14 patients (sensitivity, 29%). Results were similar to those obtained with CT (true-positive, two of seven patients [sensitivity, 29%]; true-negative, 22 of 26 patients [specificity, 85%]). FDG PET depicted liver metastases in seven of eight patients and was superior to CT, which depicted liver metastases in three patients (sensitivity of 88% and 38%, respectively). FDG PET and CT, respectively, correctly depicted the absence of liver metastases in 35 and 32 patients (specificity, 100% and 97%; negative predictive value, 97% and 86%).FDG PET has a high sensitivity and specificity for detection of colorectal carcinomas (primary and liver metastases) and appears to be superior to CT in the staging of primary colorectal carcinoma.

Noninvasive differentiation of benign from malignant disease has emerged as an important diagnostic challenge in this age of health-care cost containment. Most physicians today acknowledge that early and accurate detection of cancer is the key to successful treatment. Antibodies have been developed and used to detect and treat tumors. In the next few years, several radiolabeled antibodies will likely receive FDA approval for imaging colorectal, lung, and prostate carcinomas, thus expanding and improving the physician's ability to detect and follow cancer in patients. There is ample evidence in the literature that suggests that imaging with labeled antibodies is clinically useful for detecting colorectal cancer in patients with suspected recurrence, in patients with presumed isolated resectable liver metastasis, and in those at high risk of the development of recurrence. This paper reviews these studies, and also discusses some data obtained from positron emission tomography (PET) imaging in colorectal patients.

Approximately two-thirds of metastatic lesions that develop following curative resection of colorectal cancer occur in the liver and lung. In select groups of patients, resection of these lesions is associated with increased 5-year survival. In the liver, precise preoperative documentation of the presence, location, number, and relationship of these lesions to vascular structure is crucial in the selection of candidates for curative resection. Computed tomography with arterial portography (CTAP), intraoperative ultrasonography (IOUS), positron emission tomographic (PET) scan, and radionuclide scanning, including radiolabeled monoclonal antibody imaging, are emerging as the procedures of choice in the preoperative and intraoperative evaluation of metastatic colorectal cancer to the liver.

Beginning with Ehrlich's original “magic bullet” concept of 1904, the pioneering human trials in the late 1970s of Goldenberg and Mach using polyclonal antibodies, and the Nobel Prize-winning work of Kohler and Milstein in 1975 for developing monoclonal antibody (MAb) technology, there has been much interest in the use of antibodies for detecting and treating cancer. Although not the revolutionary breakthrough that was initially hoped for, marked progress has been made. The Food and Drug Administration (FDA) has recently approved the intact murine IgG, 111-indium CYT-103 (satumomoab, Oncoscint™ Cytogen, Princeton, NJ) for clinical use in detecting colorectal and ovarian cancer. However, the agent has been approved for only a single, one-time use, because patients developed an immune response (human anti-mouse antibody, or HAMA) that alters MAb biodistribution and may limit the clinical effectiveness of this agent when repeat studies are performed. Other MAbs reacting with a variety of antigens and targeting numerous tumors, including breast, lung, prostate, and melanomas, are currently undergoing large-scale clinical trials. To reduce induction of immune responses, many of the agents use immunoglobulin fragments [Fab, or F(ab)2] labeled with the short-lived isotope 99m-technetium used for most routine nuclear medicine diagnostic testing. Future developments will use even smaller fragments such as single chain antibodies or custom synthesized molecular recognition units (small peptides containing only the specific antigen combining site). Presented herein is an overview of the past results and an assessment of the current status of radioimmunoscintigraphy for various neoplasms.

PURPOSE: The role of immunoscintigraphy with111 Insatumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial. METHODS: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information. RESULTS: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of111 In. Thirty percent of patients developed human anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy. Occult disease was detected in 18 patients. CONCLUSION: 111 In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities.

Recent prospective clinical trials of low molecular weight heparins (LMWHs) have demonstrated that these agents may provide significant advantages in terms of progression-free and overall survival in certain subgroups of cancer patients. The mechanisms of improved survival associated with LMWHs are not known, and may involve direct and/or indirect effects on tumor growth. The purpose of this study was to investigate the effects of LMWH and a sulfated non-anticoagulant LMWH (S-NACH) on tumor chemotherapeutic uptake and chemoresponse.LMWH and S-NACH were tested for their ability to reduce tumor growth and tumor-associated angiogenesis using three different in vivo models. Biodistribution studies were undertaken to determine the effect of these agents on uptake of paclitaxel (PACL) and doxorubicin (Dox) by breast cancer tumor xenografts.LMWH and S-NACH (10 mg/kg s.c. daily) effectively limited tumor growth of human A549 lung adenocarcinoma xenografts in the nude mouse. In an MDA453/LCC6 breast tumor xenograft model, PACL plus S-NACH showed significant (p0.01) tumor growth suppression and improved survival when compared to PACL alone. LMWH increased [(124-)I]-PACL uptake into MDA453/LCC6 tumors, with tumor:muscle ratios several fold greater than that of [(124-)I]-PACL alone 24 h post-injection. Similarly, LMWH and S-NACH significantly (p0.01) increased the uptake of Dox by 1.5-2 fold in MCF7 Dox-resistant tumor xenografts.Protocols utilizing adjuvant or neo-adjuvant therapy with LMWH or S-NACH could lead to increased tumor chemo responsiveness, potentially overcoming tumor chemoresistance.

Recurrent colorectal cancer is seen in as many as 40% of patients after curative resection. In view of the limitations of endoscopic and cross-sectional imaging, external immunoscintigraphy has been added to the follow-up regimen of patients at high-risk of recurrent disease. The authors investigated the utility of immunoscintigraphy with Indium-111 (In-111) CYT-103 (site specifically labeled conjugate of monoclonal antibody B72.3) in 19 patients with suspected recurrences after previous curative resection of colorectal carcinoma. Local or regional recurrences (4 patients) and liver metastasis (6 patients) were indicated by physical examination and computed tomography (CT), whereas nine patients had occult disease with increasing serum carcinoembryonic antigen (CEA) levels and negative conventional workups. Serum CEA levels were elevated (mean, 22 ng/ml) in all patients. Approximately 4.3 mCi In-111 labeled to 1.0 mg CYT-103 was administered intravenously to each patient. Planar and single photon emission computed tomography (SPECT) imaging were performed 2-5 days after infusion. The final diagnosis of recurrence or metastasis was established in 18 patients by second-look surgery or biopsy. One patient died before exploration. Tumor was identified at the following locations: pelvis (12 patients), abdominal wall (2 patients), retroperitoneum (1 patient), liver (5 patients), and omentum (2 patients). Superiority of monoclonal antibody (MoAb) scan is noted in the detection of pelvic and intraabdominal recurrences (100%) versus CT scan (43%). Liver metastases were identified with equal facility by both modalities. In-111 CYT-103 scan findings influenced the management of 10 (55%) of 18 patients. Surgery was avoided in one patient with disseminated metastases detected by the scan. Correct identification of occult local recurrences was made in six patients. An isolated liver metastasis was confirmed in one patient with equivocal CT scan. Finally, additional intraabdominal lesions were detected in two patients. These results suggest an important and beneficial role for In-111 CYT-103 MoAb imaging in patients with suspected recurrent colorectal carcinomas, particularly in patients in whom cross-sectional imaging is negative; such imaging may prevent patients from undergoing unnecessary surgical exploration.

During the past two decades, the in vivo application of monoclonal antibodies (MoAbs) in cancer diagnosis and therapy have been widely studied. This can be related to three main factors: (1) dramatic improvement in monoclonal antibody production, revolutionized by Kohler and Milstein; (2) improvement in radioisotopes and monoclonal antibody conjugation procedure and further simplification and ease of use of these procedures; and (3) the apparent safety of single or, in selected cases, multiple administration of MoAbs to humans. The development of radioimmunoscintigraphy or radioimmunodetection has added a significant new dimension to nuclear medicine imaging, and it is very likely to broaden our approach to diagnosis and perhaps therapy of malignant diseases. The indications and limitation of radioimmunoscintigraphy must be clearly outlined to the referring oncologists and surgeons. The unique capability of radiolabeled MoAbs in detecting occult disease, upstaging patients, and, most importantly, changing patient management must be emphasized.

The most common semiquantitative method of evaluation of pulmonary lesions using 18F-FDG PET is FDG standardized uptake value (SUV). An SUV cutoff of 2.5 or greater has been used to differentiate between benign and malignant nodules. The goal of our study was to investigate the correlation between the size of pulmonary nodules and the SUV for benign as well as for malignant nodules. Methods Retrospectively, 173 patients were selected from 420 referrals for evaluation of pulmonary lesions. All patients selected had a positive CT and PET scans and histopathology biopsy. A linear regression equation was fitted to a scatter plot of size and SUVmax for malignant and benign nodules together. A dot diagram was created to calculate the sensitivity, specificity, and accuracy using an SUVmax cutoff of 2.5. Results The linear regression equations and (R2)s as well as the trendlines for malignant and benign nodules demonstrated that the slope of the regression line is greater for malignant than for benign nodules. Twenty-eight nodules of group one (≤ 1.0 cm) are plotted in a dot diagram using an SUVmax cutoff of 2.5. The sensitivity, specificity, and accuracy were calculated to be 85%, 36% and 54% respectively. Similarly, sensitivity, specificity, and accuracy were calculated for an SUVmax cutoff of 2.5 and found to be 91%, 47%, and 79% respectively for group 2 (1.1–2.0 cm); 94%, 23%, and 76%, respectively for group 3 (2.1–3.0 cm); and 100%, 17%, and 82%,, respectively for group 4 (> 3.0 cm). The previous results of the dot diagram indicating that the sensitivity and the accuracy of the test using an SUVmax cutoff of 2.5 are increased with an increase in the diameter of pulmonary nodules. Conclusion The slope of the regression line is greater for malignant than for benign nodules. Although, the SUVmax cutoff of 2.5 is a useful tool in the evaluation of large pulmonary nodules (> 1.0 cm), it has no or minimal value in the evaluation of small pulmonary nodules (≤ 1.0 cm).

18F-FDG PET is emerging as a useful tool in the staging and restaging of many malignant neoplasms, such as lymphoma, lung cancer, colorectal cancer, head and neck cancer, breast cancer, and melanoma. To accurately interpret 18F-FDG findings one must be familiar with the normal physiologic distribution of the tracer, frequently encountered physiologic variants, and benign pathologic causes of 18F-FDG uptake that can be confused with a malignant neoplasm. The objectives of this article are to (a) describe the mechanism of 18F-FDG uptake, (b) list the patient preparation and pertinent patient history before 18F-FDG imaging, (c) describe the whole-body physiologic distribution of 18F-FDG, (d) list and discuss normal physiologic variants, and (e) list and discuss benign pathologic causes of 18F-FDG uptake.

External immunoscintigraphy using a single monoclonal antibody has been employed successfully to localize primary, recurrent, and occult colorectal carcinoma. This prospective study investigated the accuracy and sensitivity of external immunoscintigraphy when the combination or "cocktail" of radiolabeled monoclonal antibodies, CYT-103 (an IgG1a) and CYT-372 (an IgG2b) directed against TAG-72 and CEA, respectively, is given to patients with known or suspected colorectal cancer.Eleven patients enrolled in this open label phase I/II study underwent preoperative external immunoscintigraphy after intravenous cocktail administration of two indium 111-labeled monoclonal antibodies (MoAb), CYT103 and CYT372. Antibody dose ranged from 0.2 mg (five patients) to 1.0 mg (six patients), each antibody radiolabeled with 2.5 mCi of indium 111, delivering a total dose of 5 mCi per patient. Planar and SPECT images were performed 2 to 5 days postinjection. Suspected lesions were surgically resected within 2 weeks of injection.A total of 23 lesions (sites) were identified in the eleven patients, 19 of which were confirmed by pathology (hematoxylin and eosin [HE]). Cocktail immunoscintigrams identified 16 of the 19 confirmed lesions. Computed tomography (CT) scan detected 9 of the 19 lesions. The sensitivities of cocktail immunoscintigraphy and CT scan for the detection of colorectal cancer were 84% and 64%, respectively. The positive predictive value for immunoscintigraphy was 94%. The antibody scans detected six occult, previously unsuspected lesions. Cocktail immunoscintigraphy changed the surgical management in four of the 11 (36%) patients.The combination of In 111 CYT-103 and CYT-372 improved the sensitivity of external immunoscintigraphy for the detection of colorectal cancer compared to that obtained with a single MoAb imaging. Cocktail antibody imaging may enhance the staging and management of patients with cancers of colon and rectum.

The aims of this prospective, nonrandomized phase I/II study were to evaluate (1) the safety and (2) the detection rate of tissue culture-derived, 111In-labelled anti-CEA monoclonal antibody IVP ZCE 025 in patients with primary, metastatic and occult colorectal carcinomas. 111In-IVP ZCE 025 imaging correctly identified 31 of 37 primary colorectal carcinomas, 10 of 19 hot liver metastases, 11 of 16 distant metastases and seven of seven local tumour recurrences. Previously unsuspected tumours were detected by IVP ZCE 025 imaging in 11 of 34 patients. The scans were also true negative in four patients. The overall performance characteristics of IVP ZCE 025 at monoclonal antibody doses of 1.0-5.0 mg were comparable to those obtained with 40.0 mg ascites-produced ZCE 025. No clinical or biochemical adverse reactions were encountered in the 61 patients entered into this study.

The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P.05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P.01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy.

Immunoscintigraphy performed after intravenous administration of indium-111-labeled CYT-103, an immunoconjugate of monoclonal antibody B72.3, was evaluated in patients with suspected primary or recurrent colorectal cancer at 25 centers in the United States. Gamma camera imaging, computed tomography (CT), and confirmatory surgical exploration were completed in 169 of 227 patients who received single infusions of In-111 CYT-103. Eight patients (3.5%) had reversible, nonserious adverse reactions, and 39% developed antimurine antibodies. Surgery revealed that 155 of 169 patients had colorectal carcinoma. In these 155 patients, immunoscintigraphy and CT demonstrated similar sensitivity (69% and 68%, respectively) and specificity (77%). However, immunoscintigraphy had greater sensitivity in detection of pelvic tumors (74% vs 57%, P = .035) and extrahepatic abdominal tumors (66% vs 34%, P less than .001); CT enabled detection of a greater proportion of liver metastases (84% vs 41%, P less than .001). These results indicate that In-111 CYT-103 can be administered safely and that immunoscintigraphy performed with this agent frequently enables identification of extrahepatic abdominal sites of disease not visualized with CT.

A phase 1 study was conducted with the investigational immunoscintigraphic agent, 111In-CYT-356, a radiolabeled, site-specific immunoconjugate of monoclonal antibody 7E11-C5.3, in 40 patients with prostatic carcinoma and known distant metastases. Each patient received a single intravenous infusion of CYT-356 (dose range, 0.1-5 mg) radiolabeled with approximately 5 mCi of 111In. None of the patients experienced adverse reactions. One patient who received a 5-mg dose developed antibodies to the CYT-356 immunoconjugate. 111In-CYT-356 immunoscintigraphy detected bony metastases in 21 of 38 patients (55%), including 12 of 14 (86%) receiving concomitant hormonal therapy, and soft tissue lesions in four of six patients (67%). Antibody imaging detected occult lesions in the bony pelvis and lumbar spine, which were confirmed by follow-up imaging tests, in one patient. Higher CYT-356 doses may clear the blood pool more slowly. These results suggest that 111In-CYT-356 can be safely administered to patients with prostatic carcinoma and that further clinical investigation of this agent is warranted.

• B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111–labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111–labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111–labeled scanning of B72.3 directly affected treatment in 18% of patients. ( Arch Surg . 1990;125:1601-1605)

• We investigated the utility of scanning with indium 111 labeled to monoclonal antibody in 13 patients after curative resection of colorectal cancer who had elevated carcinoembryonic antigen levels and negative results of clinical workup. Each patient received 1 mg of anti–carcinoembryonic antigen monoclonal antibody type ZCE 025 labeled with 5.5 mCi of111In, plus 9 to 39 mg of the same antibody unlabeled. Patients underwent scanning 3 to 7 days after infusion by planar and emission computed tomography. ZCE-025 monoclonal antibody imaging detected tumor recurrence or metastasis in 11 of 13 patients. In one patient the monoclonal antibody scan gave a true-negative result, and in one patient the monoclonal antibody scan failed to disclose a metachronous cecal primary. Tumor sites identified were the pelvis (2 patients), abdominal wall (2), retroperitoneum (1), lymph nodes (3), liver (2), bone (2), and lung (1). The accurate localization of colorectal carcinoma recurrences by means of111In ZCE-025 monoclonal antibody demonstrates the usefulness of this diagnostic agent in the setting of elevated carcinoembryonic antigen level and negative results of clinical and radiologic workup. (Arch Surg. 1990;125:226-229)

The localization of In-111 labeled leukocytes (WBCs) in recent surgical incisions was studied in 18 patients. In-111 WBC images correlated well with culture results and clinical findings. No accumulation of In-111 WBCs was detected at the site of noninfected incisions in nine patients. In-111 WBCs did accumulate at incision sites in nine patients with infected surgical incisions. These results indicate that In-111 WBC study can accurately distinguish between normal healing and infection of recent surgical incisions.

Localization of Huerthle cell cancer deposits in the lung with I-131 labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody is described. This technique may prove useful if conventional scanning with I-131 sodium iodide for distant metastases is negative.

We reviewed our experience with thyroid sonography of 60 patients with nonfunctioning (cold) solitary thyroid nodules proven by iodine 123 scan. Twenty-two patients had surgery; the remaining 38 had thyroid scan and ultrasound only. In the first group, the echograms did not demonstrate the surgically proven nodules in seven patients (32%). In the second group, the thyroid echograms were reported as negative in 12 patients (32%). Two of these patients had computerized tomography (CT) which confirmed the solitary nodule identified on the 123I scan. As a consequence, we no longer perform or recommend routine thyroid echograms on all scintigraphically cold solitary nodules. We believe that the extra cost of a thyroid echogram is not justified and that the most rational application of thyroid ultrasonography is in assessing the response of a nodule to suppressive hormonal therapy.

One of the major disadvantages of the use of 131I in the treatment of thyrotoxicosis is the development of hypothyroidism. Alternatively, 125I has been proposed for thyrotoxicosis therapy, and was thought to be preferable to 131I because of the short range of its emitted soft electrons. Several studies have shown 125I to be as effective as 131I in the treatment of thyrotoxicosis, and equally likely to produce hypothyroidism. This work compared the radiobiological effects of 131I and 125I given in doses to deliver the same amount of radiation to the rat thyroid gland. These effects were studied by in vivo determination of single-strand DNA breaks by alkaline sucrose gradient sedimentation using the DABA fluorescent technique to detect the DNA. Serum T4 and TSH concentrations and percentage T3 uptake were determined by RIA. The incidence of hypothyroidism following 131I and 125I therapy was found to be the same (10% in each group). The extent of DNA damage following 125I therapy was greater than the damage induced by a larger dose of 131I.

To the Editor. —Hyperthyroidism with poor or no radioactive iodine 123 uptake on thyroid scanning may be found with subacute thyroiditis, silent thyroiditis, or factitious thyrotoxicosis.1-5Factitious thyrotoxicosis can usually be confirmed by the administration of thyrotrophin (thyroid-stimulating hormone) showing thyroid gland incorporation of radioactive iodine 123. We recently encountered a patient who had factitious thyrotoxicosis in whom a technetium Tc 99m pertechnetate thyroid scan helped to establish the diagnosis. Report of a Case. —An 18-year-old woman was referred to the Ohio State University Hospitals, Columbus, because she suffered from self-induced vomiting, amenorrhea, and anorexia nervosa of three months' duration. On physical examination, she weighed 39.6 kg, and her pulse rate was 60 beats per minute. There was no goiter, and she was clinically euthyroid despite a serum total thyroxine level of 22 μg/dL and an elevated free thyroxine index that was repeated on several occasions. The thyroid-stimulating