Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells.

BACKGROUND: The sequence of the beta-subunit of human chorionic gonadotropin (hCGß) varies depending on whether hCGß is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCGß can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCGß encoded by type II genes (type II hCGß). METHODS: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCGß dosing immunoassays and sequencing of CGB genes were performed. RESULTS: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCGß derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and T24 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCGß. Placenta immunohistochemical studies confirmed that type II hCGß expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCGß in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. CONCLUSION: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.

A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer.

PURPOSE: To investigate the dose-response relationship and pain-relieving effect of radium-223, a highly bone-targeted alpha-pharmaceutical. METHODS: One hundred patients with castration-resistant prostate cancer (CRPC) and painful bone metastases were randomized to a single intravenous dose of 5, 25, 50 or 100 k Bq/kg radium-223. The primary end-point was pain index (visual analogue scale [VAS] and analgesic use), also used to classify patients as responders or non-responders. RESULTS: A significant dose response for pain index was seen at week 2 (P = .035). At week 8 there were 40%, 63%, 56% and 71% pain responders (reduced pain and stable analgesic consumption) in the 5, 25, 50 and 100 k Bq/kg groups, respectively. On the daily VAS, at week 8, pain decreased by a mean of -30, -31, -27 and -28 mm, respectively (P = .008, P = .0005, P = .002, and P < . 0001) in these responders (post-hoc analysis). There was also a significant improvement in the brief pain inventory functional index for all dose-groups (P = .04, .01, .002 and .02, Wilcoxon signed rank test). Furthermore, a decrease in bone alkaline phosphatase in the highest dose-group was demonstrated (P = .0067). All doses were safe and well tolerated. CONCLUSION: Pain response was seen in up to 71% of the patients with a dose response observed 2 weeks after administration. The highly tolerable side-effect profile of radium-223 previously reported was confirmed.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging in the staging and prognosis of inflammatory breast cancer.

BACKGROUND: : To prospectively assess fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging and prognosis value in patients with suspected inflammatory breast cancer (IBC). METHODS: : Sixty-two women (mean age 50.7 +/- 11.4 years) presenting with unilateral inflammatory breast tumors (59 invasive carcinomas; 3 mastitis) underwent a PET/CT scan before biopsy. RESULTS: : PET/CT scan was positive for the primary malignant tumor in 100% and false positive in 2 of 3 benign mastitis. In 59 IBC patients, FDG nodal foci were detected in axillary (90%; n = 53) and extra-axillary areas (56%; n = 33) ipsilateral to the cancer. Compared with clinical examination, the axillary lymph node status by PET/CT was upstaged and downstaged in 35 and 5 patients, respectively. In 7 of 9 N0 patients, the axillary lymph node positivity on PET/CT was correct, as revealed by pathological postsurgery assessment (not available in the 2 remaining patients). The nodal foci were compared with preoperative fine needle aspiration and/or pathological postchemotherapy findings available in 44 patients and corresponded to 38 true positive, 4 false-negative, and 2 false-positive cases. In 18 of 59 IBC patients (31%), distant lesions were found. On the basis of a univariate analysis of the first enrolled patients (n = 42), among 28 patients who showed intense tumoral uptake (standard uptake value(max)>5), the 11 patients with distant lesions had a worse prognosis than the 17 patients without distant lesions (P = .04). CONCLUSIONS: : FDG-PET/CT imaging provides additional invaluable information regarding nodal status or distant metastases in IBC patients and should be considered in the initial staging. It seems also that some prognostic information can be derived from FDG uptake characteristics. Cancer 2009. (c) 2009 American Cancer Society.

[Pain and bone metastases]. / Douleur et métastases osseuses.

Average 20% of the cancer patients will have bone metastasis most of time painful and with variable clinical expressions. Due to animal models, the bone metastasis pain is better known and it explains the different treatments mechanisms. After a suitable evaluation of the pain, several therapeutic approaches can be suggested. In addition to the classical analgesics, several medications are known to be efficient in few indications like neuropathic pain. Besides a local surgery, an external radiotherapy or an interventional radiology treatment can often be useful along with a medical treatment. When there is a bone progression, the anti-cancer treatment by chemotherapy, hormonotherapy or targeted therapies must always be reviewed, because if efficient it could have an analgesic action.

Relationship between lymphoscintigraphy and clinical findings in lower limb lymphedema (LO): toward a comprehensive staging.

Although radionuclide lymphoscintigraphy (RNL) is widely used diagnostically for patients with lymphedema (LE), it has not been utilized for LE staging, which is still based upon clinical findings. The aim of this work is to establish whether the results of both conventional RNL and fusion imaging obtained from hybrid detectors may be used for a comprehensive clinicoimaging staging in LE. Radiolabeled nanocolloids (0.2 ml) were subcutaneously injected in 4,328 patients (23-78 years) with clinical lower limb LE and without venous disease. Patients were classified according to the ISL classification and had a minimal follow-up of 2 years. Images were taken 60 minutes after the injection as a whole body scanning and fusion images of functional SPET and anatomical CT. Clinical and RNL results were not in accordance, and a specific RNL staging was established. The association of clinical and functional staging yields a new method to grade LE patients, and this staging correlated with treatment efficacy. RNL is an important tool in lymphology, and its association with the clinical evaluation offers a new grading system which may be able to delineate patients with good prognosis, patients at risk for a complex decongestive physiotherapy (CDP) failure, and patients who may benefit from other therapeutic protocols.

Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts.

Trophoblast research over the past decades has underlined the striking similarities between the proliferative, migratory and invasive properties of placental cells and those of cancer cells. This review recapitulates the numerous key molecules, proto-oncogenes, growth factors, receptors, enzymes, hormones, peptides and tumour-associated antigens (TAAs) expressed by both trophoblastic and cancer cells in an attempt to evaluate the genes and proteins forming molecular circuits and regulating the similar behaviours of these cells. Among the autocrine and paracrine loops that might be involved in the strong proliferative capacity of trophoblastic and cancer cells, epidermal growth factor (EGF)/EGF receptor (EGFR), hepatocyte growth factor (HGF)/HGF receptor (HGFR) (Met) and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) loops may play a predominant role. Similar mechanisms of migration and invasion displayed by trophoblastic and malignant cells comprise alterations in the adhesion molecule phenotype, including the increased expression of alpha1beta1 and alphavbeta3 integrin receptors, whereas another critical molecular event is the down-regulation of the cell adhesion molecule E-cadherin. Among proteases that may play an active role in the invasive capacities of these cells, accumulating evidence suggests that matrix metalloproteinase-9 (MMP-9) expression/activation is a prerequisite. Finally, an overview of molecular circuitries shared by trophoblast and cancer cells reveals that the activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT axis has recently emerged as a central feature of signalling pathways used by these cells to achieve their proliferative, migratory and invasive processes.

Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide assays and radionuclide ventriculography.

BACKGROUND: To study the longitudinal variations of plasma B-type natriuretic peptide (BNP) with reference to left ventricular ejection fraction (LVEF) during and after chemotherapy with cardiotoxic drugs. PATIENTS AND METHODS: We prospectively measured plasma BNP using an immunoradiometric assay in 12 anthracycline-treated breast cancer patients monitored for a mean time of 880+/-293 days (pilot group). Prior to each cycle and throughout the following year, LVEF and cardiac output were measured by radionuclide ventriculography. Anthracycline pharmacokinetics was studied during the first cycle. Relationships between serial observations were analysed with the general linear mixed effects model. Identical methods were subsequently applied to a test group of 67 anthracycline or trastuzumab-treated patients. RESULTS: Five out of 70 (6.33%) patients developed anthracycline-induced heart failure. BNP concentrations were found to be positively correlated to anthracycline cumulative dose and negatively to LVEF values. Variables entering the mixed models were cumulative anthracycline dose, time and cardiac output. CONCLUSION: An infra-clinical cardiotoxicity of anthracyclines as defined by BNP elevation is frequent but reversible. Patients who developed heart failure showed a continuous BNP increase and concentrations over 100 ng/ml.

Efficacy of BN165 (Ginkor Fort) in breast cancer related upper limb lymphedema: a preliminary study.

The purpose of this study was to determine whether BN165 (Ginkor Fort), which has been reported to alleviate symptoms of venous insufficiency, has a beneficial effect on lymphatic function or lymphedema symptoms. Using a 3-arm, double-blind, placebo-controlled design in 48 patients with upper extremity lymphedema secondary to breast cancer treatment, improvement in symptoms and signs as well as lymphoscintigraphic kinetic parameters (radiocolloid half-life and lymphatic migration speed) was assessed in response to treatment. A statistically significant effect on limb heaviness was noted. Lymphatic migration speed also demonstrated a significant increase at a dose of 2 active capsules per day but not at the 3 capsules per day dose, but lymphatic migration speed also improved in the placebo group. These findings in mechanical lymphatic insufficiency in breast cancer-related lymphedemas can be compared to the previously published clinical amelioration by BN165 of the subjective symptoms (heavy limbs) of dynamic lymphatic insufficiency in patients with venous insufficiency. Further studies are needed to define the possible role of BN165 in treating patients with lymphedema.

[Comparative analysis of lymphoscintigraphy between lipedema and lower limb lymphedema]. / Analyse comparative de la lymphoscintigraphie au cours des lipoedèmes et des lymphoedèmes primitifs des membres inférieurs.

UNLABELLED: Lipedema is characterized by bilateral enlargement of the legs due to abnormal deposition of fat tissue from pelvis to ankles. It is seen most frequently in obese women. Lipedema appears to be a distinct clinical entity but may be confounded with lymphedema. AIM OF THE STUDY: To analyze and to compare between lipedema and lymphedema the qualitative and quantitative aspects of lymphoscintigraphy. METHODS: Fifteen women with lipedema were recruited. Mean age of onset of lipedema was 31.5 +/- 15 years. Body mass index was 35.1 +/- 7.9 kg/m2, 13 women were obese. Lipedema was compared to 15 cases of primary lymphedema (women: 13, men: 2) of the lower limbs (unilateral: 13, bilateral: 2), with a mean age at onset of 28.7 +/- 12.6 years. Lymphoscintigraphy of the lower limbs with morphologic (visualization of inguinal lymph nodes) and kinetic (half-life, lymphatic speed of the colloid) studies was performed in all cases. RESULTS: Absence of visualization of inguinal lymph nodes was observed in 14/15 cases of lymphedema and in 1/15 cases of lipedema (p<0.001). In the 13 cases of unilateral lymphedema, colloid half-life was higher in the pathologic limb than in the controlateral limb (230 +/- 92 vs 121 +/- 36 minutes, p<0.01) and lymphatic speed of the colloid was slower (6.91 +/- 0.86 vs 8.16 +/- 1.02 cm/min, p<0.001). The two patients with bilateral lymphedema had an increased half-life and decreased lymphatic speed of the colloid. Colloid half-life was significantly higher in lipedema than in controlateral limbs of lymphedema (154 +/- 23 vs 121 +/- 36 minutes, p<0.01) with no difference in lymphatic speed of the colloid. Colloid half-life was significantly higher in lymphedema than in lipedema (230 +/- 92 vs 154 +/- 23 minutes, p<0.01) and the lymphatic speed of the colloid was slower (6.91 +/- 0.86 vs 8.10 +/- 0.45 cm/min, p<0.001). CONCLUSION: Lower limb lymphoscintigraphy showed lymphatic insufficiency in lipedema without morphologic abnormality as seen in lymphedema. Lymphoscintigraphy is not indispensable but is a useful tool when diagnosis is doubtful. Treatment is difficult and may include weight loss and possible surgery.

[Tests and imaging of the lymphatic system]. / Explorations et imagerie du système lymphatique.

Methods for lymphatic imaging are numerous and can be roughly classified as anatomic or functional studies. Direct or indirect lymphographies provide useful informations in case of lymphostasis. Contrast lymphangiography is the only anatomical method giving precise informations either on lymphatic ducts or lymph nodes. Nevertheless this invasive method is no more indicated in cases of limb edemas. Indirect lymphographies study the spontaneous lymphatic drainage of inert particles injected into the dermis. The blue dye test is the most simple and the oldest indirect lymphography used in the positive diagnosis of a lymphostasis. It has been replaced with the indirect radionuclide lymphography which give more reliable informations. Fluorescence microlymphoangiography is an atraumatic method which permits the visualization of skin lymphatics. Indirect lymphangiography with contrast medium give reliable informations on the status of the initial lymphatics and is the best imaging method to differentiate between lipedema and lymphedema. Indirect radionuclide lymphoscintigraphy is a safe, non invasive and physiological method for the assessment of the limb lymphatic system used for morphological studies and objective measurement of the peripheral lymphatic function necessary to assess the lymphatic variation under therapy (decongestive physiotherapy, surgery, drugs).

Positron emission tomography detection of breast cancer metastasis to the uterus.

BACKGROUND: We report the case of a patient presenting with moderate elevation of the tumor marker cancer antigen 15.3 during breast cancer follow-up. CASE: After a negative standard metastatic work-up, a positron emission tomography scan identified a localized central pelvic zone of uptake. Hysterectomy was performed, and pathology revealed a breast cancer metastasis within a previously known uterine leiomyoma. Positron emission tomography allowed assessment of soft tissues. CONCLUSION: With high sensitivity and specificity, positron emission tomography can be used to localize breast cancer metastases suspected by the presence of elevated serum tumor marker but not detected on standard metastatic workup.

Detection of occult disease in breast cancer using fluorodeoxyglucose camera-based positron emission tomography.

An isolated increase of blood tumor marker CA 15.3 in breast cancer is considered a sensitive indicator for occult metastatic disease but by itself is not sufficient for initiating therapeutic intervention. We investigated the potential of camera-based positron emission tomography (PET) imaging using [18F]-fluorodeoxyglucose (FDG) to detect clinically occult recurrences in 132 female patients (age, 35-69 years) treated for breast cancer, all presenting with an isolated increase in blood tumor marker CA 15.3 without any other evidence of metastatic disease. FDG results were correlated to pathology results or to a sequentially guided conventional imaging method. One hundred nineteen patients were eligible for correlations. Positive FDG scans were obtained for 106 patients, including 89 with a single lesion and 17 with 2 or more lesion. There were 92 true-positive and 14 false-positive cases, 10 of which became true positive within 1 year. Among the 13 negative cases, 7 were false negative and 6 were true negative. Camera-based PET using FDG has successfully identified clinically occult disease with an overall sensitivity of 93.6% and a positive predictive value of 96.2%. The smallest detected size was 6 mm for a lymph node metastasis (tumor to nontumor ratio, 4:2). FDG camera-based PET localized tumors in 85.7% of cases suspected for clinically occult metastatic disease on the basis of a significant increase in blood tumor marker. A positive FDG scan associated with an elevated CA 15.3 level is most consistent with metastatic relapse of breast cancer.

Serum chromogranin-A in advanced prostate cancer.

OBJECTIVE: To determine the value of serum chromogranin A (CgA), a marker of neuroendocrine differentiation, for monitoring prostate cancer: CgA levels were related to three other tumour markers, i.e. total prostate-specific antigen (tPSA), prostatic acid phosphatase (PAP), neurone-specific enolase (NSE), and to testosterone, to assess the importance of hormone withdrawal. PATIENTS AND METHODS: Serum samples (218) were obtained from 118 patients with prostate cancer, including 111 patients with advanced prostate cancer: 103 presented to our centre for systemic radionuclide therapy of painful skeletal metastases. CgA concentrations were measured using a new immunoradiometric assay (IRMA: Cis Bio International, Gif sur Yvette, France) and a threshold of 70 ng/mL was determined after receiver operating characteristic curve analysis. Testosterone was also measured with an IRMA assay; tPSA, PAP and NSE were assayed using the time-resolved amplified cryptate emission. RESULTS: Serum marker levels were high in 64% of the patients for CgA, 24% for NSE, 89% for tPSA and 81% for PAP. Patients resistant to endocrine treatments and with elevated tPSA (i.e. hormone-independent) showed increased CgA and NSE in 62% and 29%, respectively. Patients with hormone-dependent prostate cancer (i.e. with a normal tPSA level) had elevated CgA in 59% but no abnormal NSE. All patients of the latter group except one showed clinical progression of their disease. However, the mean (SD) concentrations of CgA in hormone-independent (146) or hormone-dependent (22) patients, at 185.3 (449.1) and 160.9 (293.9) ng/mL, respectively, were not statistically different (P=0.8, Mann-Whitney U-test). For 30 patients, blood samples were drawn and markers measured before and after systemic radionuclide therapy. There was a significant increase in the CgA and tPSA concentrations after treatment (P=0.0146 and 0.0025, respectively). CONCLUSIONS: In association with tPSA, serum CgA appears to be a promising marker for monitoring patients with prostate cancer.

Serum bFGF (basic fibroblast growth factor) and CA 15.3 in the monitoring of breast cancer patients.

BACKGROUND: Basic fibroblast growth factor (bFGF) is a potent angiogenetic factor which may influence breast cancer evolution. MATERIALS AND METHODS: Serum bFGF, (cut-off 10 pg/ml), was assayed in 166 breast cancer patients at all stages and compared with CA 15.3. RESULTS: In 99 pre-treatment (PT) sera, 39/99 (39.4%) were bFGF positive, 9/99 (9.1%) CA 15.3 positive (> 30 U/ml), and not correlated. No correlations were found between bFGF and age, menopausal status, TNM or pTNM, histology, SBR grading or steroid receptors. A postoperative decline in bFGF positivity, from 30.8 to 7.7% (n = 39), was observed. An abnormal CA 15.3 after primary treatment (n = 2/39) was of bad prognosis (P < 0.0001), whereas positive bFGF (n = 3/39) had no univariate prognostic value (median follow-up 5.5 years). During follow-up, positive bFGF was recorded in 6/92 (6.5%) disease-free patients (DFS), 13/15 (86.7%) regressions, 8/16 (50.0%) stable disease, and 46/67 (68.7%) progressive disease (significant differences between PT or DFS and post recurrence levels (P < 0.001), and between relapse before and after treatment (P = 0.002)). CONCLUSION: Serum bFGF is more often elevated before treatment or after relapse than in DFS, and rises under systemic treatments. Its pattern of variations does not add to CA 15.3 for breast cancer monitoring.

[1959-1999: from serum markers to 18-FDG in oncology. The experience of the René-Huguenin Center]. / 1959-1999: des marqueurs sériques au 18-FDG en oncologie. L'expérience du centre René-Huguenin.

Blood tumour markers are widely used in the follow up of patients treated for a malignant tumour. In many cases where the tumour associated marker is increasing the clinical and radiological evaluations remain normal. PET and CDET-scan with 18-FDG have been demonstrated as powerful tools in oncology and their use in such situations may give a new appraisal on the development of the disease. Seventy patients with an isolated increasing of a tumour associated marker (CEA or CA19.9, CA15.3, CA125) were tested. Accuracy and sensitivity of the method were 82.8 and 96.5%, specificity 25%, and positive and negative predictive values 50% and 87%. Focusing on breast carcinomas and CA15.3 as well as ovarian cancers and CA125, the sensitivity and the predictive value are reaching 100%. Patients exhibiting a tumor target associated to an increasing in blood tumour marker may be treated earlier with dedicated protocols.

Possibilities and restriction of isotopic lymphography for the assessment of therapeutic effects in lymphedema.

Whatever the results are, we must keep in mind that the method used must be safe, simple, reproductive, quite physiological. The RNL with distal registration during 40 min give more precise and reliable informations particularly in transient or permanent lymphatic dysfunctions. This should be the protocol used for the assessment of the lymphatic function and the treatment efficacy. The RNL with nodal uptake registration is totally related to the lymphatic transport from the extremities and the exercise applied. When performed by well trained physicians concerned with the lymphatic physiology and informed of all factors interfering with the results, the quantitative functional lymphoscintigraphy is really giving objective and reproductive parameters to evaluate a treatment efficacy (decongestive physiotherapy, surgery, drugs) in lymphedemas useful to assess new lymphotonic treatments.

Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium Tc 99m 88BV59H21-2V67-66 (HumaSPECT-Tc), a totally human monoclonal antibody. Patient management benefit from a phase III multicenter study.

PURPOSE: The study contained herein was undertaken to evaluate the accuracy of radiolabeled human monoclonal antibody, 88BV59H21-2V67-66 (88BV59 or HumaSPECT-Tc), in predicting disease resectability in presurgical subjects with recurrent, metastatic, or occult colorectal carcinoma. METHODS: A total of 219 patients with disease visualized on computed tomographic scan (recurrent or metastatic disease) or with negative or equivocal computed tomographic scan and rising carcinoembryonic antigen serum levels (occult group) received technetium Tc99m-labeled 88BV59 intravenously. Planar and single photon emission computed tomograhic images were obtained 14 to 20 hours postinfusion, before surgery. The ability of computed tomographic and HumaSPECT-Tc imaging to define the extent of disease and to predict resectability was evaluated based on surgical and histopathologic results. RESULTS: In patients with recurrent or metastatic disease (170 evaluable patients), the accuracy of predicting nonresectability of disease was significantly greater (P < 0.001) for HumaSPECT-Tc than for computed tomography (60 vs 29 percent). Computed tomography understaged 41 percent of patients believed to have resectable disease compared with 27 percent for HumaSPECT-Tc (P < 0.001). In occult disease patients (29 computed tomographic and 28 HumaSPECT-Tc evaluable patients), the overall accuracy of predicting resectability/nonresectability was 6 percent for HumaSPECT-Tc compared with 24 percent from computed tomography. Administration of HumaSPECT-Tc had no effect on monoclonal antibody-based in vitro diagnostic assays. Only a single patient demonstrated an anti-antibody response (90 ng/ml) at nine weeks postinfusion. CONCLUSION: HumaSPECT-Tc was more accurate than computed tomography in determining disease resectability in patients with metastatic, recurrent, or occult cancer. The addition of HumaSPECT-Tc imaging can play a significant role in patient management decisions.

Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99m-labeled totally human monoclonal antibody 88BV59: results of pivotal, phase III multicenter studies.

PURPOSE: To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer. METHODS: 88BV59, labeled with technetium Tc 99m (99mTc) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated. RESULTS: All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human anti-human antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed. CONCLUSION: HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans.