The pharmacokinetics of ¹³¹I-rituximab in a patient with CD20 positive non-Hodgkin Lymphoma: evaluation of the effect of radioiodination on the biological properties of rituximab.

PURPOSE: To report the pharmacokinetics of ¹³¹I-rituximab a patient with a CD20 positive non-Hodgkin Lymphoma who has received ¹³¹I-rituximab as consolidation treatment after remission induction and to evaluate the effect of radioiodination on the biological properties of rituximab. RESULTS: The patient was a 65-year-old male with a relapsed CD20 positive follicular non-Hodgkin Lymphoma. After induction therapy the patient was in partial remission. Following administration of a diagnostic dose of 185 MBq ¹³¹I-rituximab, remaining lesions were identified on the wholebody scans. The patient then received a therapeutic dose of 1000 MBq ¹³¹I-rituximab. The uptake by the tumor in the right axilla was 0.17-0.21% of the injected dose. The calculated biological half-life of ¹³¹I-rituximab was 684 hrs. This biological half-life corresponded well with the half-life of unlabeled rituximab which was approximately 720 hrs. DISCUSSION AND CONCLUSION: Even though radioiodination of rituximab results in a reduced binding capacity, whole body scans demonstrated localization of ¹³¹I-rituximab in the tumor area. This observation supports the specific targeting of ¹³¹I-rituximab. The half-life of ¹³¹I-rituximab corresponded to the half-life of unlabeled rituximab. Hence, the pharmacokinetics of ¹³¹ I-rituximab was not relevantly affected by the radioiodination process.

[Added value of prone position technique for PET-TAC in breast cancer patients]. / Valor añadido de la técnica en decúbito prono para el estudio con tomografía por emisión de positrones-tomografía computarizada en las pacientes con cáncer de mama.

AIM: This study has aimed to assess if the prone position shows significant differences in regards to the supine position in PET/CT studies in breast cancer patients and to determine which modality offers better evaluation of the images. METHOD: A total of 30 patients were included from October 2009 to February 2010 prior to beginning neoadjuvant chemotherapy. An intravenous (18)F-FDG dose ranging from 180 to 240 MBq was administered. Image acquisition was begun 60 ± 10 min after injection. First of all, a thorax scan was performed with the patient in prone position, followed by a whole body study with the patient in supine position. RESULTS: Uptake in tumor lesions was observed in all of the patients. Twenty-four patients (80%) had the same number of lesions with both techniques. Five patients (17%) had a different amount of axillary lymph nodes. One patient (3.3%) had a different number of lesions. The prone position lesions had a mean SUVmax 8.89 ± 4.18 compared to 7.67 ± 4.34 in supine position. The areas of the primary breast lesions were higher in the prone position (8.59 ± 7.80 compared with 7.81 ± 7.39). Mean SUVmax of axillary nodes was 5.97 ± 4.02 in prone and 4.41 ± 3.10 in supine. CONCLUSION: The hanging breast technique can achieve higher lesion visualization as well as higher semiquantitative values in comparison with standard procedure. This supports its inclusion in acquisition guidelines of PET/CT imaging in breast cancer patients.

Intraoperative radioguidance with a portable gamma camera: a novel technique for laparoscopic sentinel node localisation in urological malignancies.

PURPOSE: Our aim was to assess the feasibility of intraoperative radioguidance with a portable gamma camera during laparoscopic sentinel node (SN) procedures in urological malignancies. METHODS: We evaluated the use of the intraoperative portable gamma camera in 20 patients: 16 patients with prostate carcinoma (PCC), 2 patients with renal cell carcinoma (RC) and 2 patients with testicular cancer (TC). Intra/peritumoural injection of (99m)Tc-nanocolloid ((99m)Tc) was followed by planar lymphoscintigraphy, SPECT/CT and marking of SN levels. Before laparoscopy a (125)I seed was fixed on the laparoscopic gamma probe as a pointer of SN seeking. The portable gamma camera was set to display the (99m)Tc signal for SN localisation and the (125)I signal for SN seeking. Matching of these signals on screen indicated exact SN localisation, and consequently this SN was removed. RESULTS: The mean injected dose was 218 MBq in PCC, 228 MBq in RC and 88 MBq in TC. Pelvic SN were visualised in all PCC patients, with uncommonly located SN in seven patients. SN metastases were found in seven patients (one in a uncommonly located SN). Both RC patients and TC patients had para-aortic SN, which were all tumour free. A total of 59 SN were removed. The portable gamma camera enabled real-time SN display/identification in 18 patients (90%). CONCLUSION: The use of a portable gamma camera in combination with a laparoscopic gamma probe incorporates intraoperative real-time imaging with improved SN identification in urological malignancies. This procedure might also be useful for SN identification of other deep draining malignancies.

[Regional lymph nodes at a distance]. / Regionale lymfekliergebieden op afstand.

In 3 patients, two men aged 22 years and 38 years with melanoma, and one woman aged 46 years with breast cancer, local tumour growth recurred following regional lymph node dissection. All three developed metastasis in new distant regional basins, which were once more dissected. The first melanoma patient died from haematogenous metastasis, 2 years after the excision of his primary melanoma. The other melanoma patient was alive, without evidence of disease, 8 years after the treatment of his primary tumour. The breast cancer patient, who underwent contralateral axillary lymph node dissection, was also alive, without evidence of disease, 27 years after the treatment of her primary tumour. Diversion of lymphatic flow as a result of regional lymph node dissection for cancer may lead to metastasis to a distant lymph node basin if tumour growth recurs in the original area. Knowledge of this usually unknown phenomenon is important since metastasis to these new regional basins can still be treated curatively, in the form of another lymph node dissection. These distant lymph node basins must therefore be carefully checked during follow-up monitoring.

Radionuclide Imaging of Apoptosis in Malignancies: Promise and Pitfalls of Tc-Hynic-rh-Annexin V Imaging.

Radionuclide detection of apoptosis with of (99m)Tc-Hynic-rh-Annexin V scintigraphy is an effective tool for in vivo visualisation and monitoring of apoptosis in various malignant tumour. Early therapy-induced increase of the tumour tracer uptake correlates with favourable outcome, whereas stable or decreased uptake correlates with stable disease or tumour progression. Therefore sequential (99m)Tc-Hynic-rh-Annexin V scintigraphy could be used to predict therapy outcome on a patient-to-patient basis within 48 hours after the start of treatment. However, moderate tumour-to-background ratio and therapy-induced changes in normal tissues could confound image analysis. To assure accurate interpretation of Annexin V scans, the awareness of the biophysiological and biochemical properties contributing to the tracer distribution is essential. In with manuscript we discuss the patterns of Annexin V tumour uptake and illustrate the most frequent pitfalls associated with Annexin V imaging in correlation with CT and MRI imaging.

Excision biopsy of breast lesions changes the pattern of lymphatic drainage.

BACKGROUND: The aim was to validate the sentinel node biopsy procedure in women who had previous breast excision biopsy by means of determining the reproducibility of lymphoscintigraphy after surgery. METHODS: Twenty-five women scheduled for excision biopsy of a breast lesion were investigated. The day before surgery, (99m)Tc-labelled nanocolloid was injected into the tumour. Lymphoscintigraphy was repeated a minimum of 2 weeks after surgery. RESULTS: Preoperative lymphoscintigraphy visualized at least one sentinel node in all 25 women. Discrepancy in the drainage patterns after surgery was noted in 17 of 25 patients. A change in the drainage pattern in the axilla after excision biopsy was seen in 11 women. Drainage to the internal mammary chain was noted before surgery in 13 women, but only three had the same drainage pathways after excision biopsy. CONCLUSION: After breast excision biopsy lymphoscintigraphy usually showed a different drainage pattern. This implies that sentinel node biopsy should be performed before excision biopsy to ensure optimal sensitivity.

Serum hemoglobin levels predict response to strontium-89 and rhenium-186-HEDP radionuclide treatment for painful osseous metastases in prostate cancer.

OBJECTIVE: Retrospective comparative analysis of strontium-89 chloride (Sr89) and rhenium-186-hydroxyethylidene diphosphonate (Re186-HEDP) radionuclide treatment to find predictors of response in patients with painful metastases from hormone refractory prostate cancer. PATIENTS AND METHODS: Clinical data from 60 hormone refractory PCA patients (i.e. rising PSA at castrate testosterone serum levels) was obtained. Twenty-nine were treated with Sr89, 31 were treated with Re186-HEDP for painful osseous metastasis. Response was defined as a patient-reported decrease in pain and/or reduction in pain medication with stable pain level. Hematological parameters and serum levels of PSA, alkaline phosphatase, and lactate dehydrogenase were assessed prior to and at 4-week intervals after treatment. RESULTS: Median survival of all patients was 7 months (95% CI: 6-9 months). Overall, 33/60 (55%) patients reported a decrease in pain after the first radionuclide treatment. This percentage was similar for patients treated with Re168-HEDP and Sr89. Mean duration of reported pain response was 75 days (+/- 68 days) for Sr89 and 61 days (+/- 56 days) for Re186-HEDP, which was not significantly different. A lower blood hemoglobin concentration was associated with a lower pain response rate. In a multivariate Cox regression analysis, pain response to radionuclide treatment predicted longer survival after treatment. CONCLUSIONS: Pain response was present in 55% of patients. Serum hemoglobin concentration prior to radionuclide treatment predicted pain response for both Re186-HEDP and Sr89. A reduction in pain upon radionuclide treatment was associated with a longer survival after treatment.

Interferon and meta-iodobenzylguanidin combinations in the treatment of metastatic carcinoid tumours.

Interferon (IFN) and meta-iodobenzylguanidin (MIBG) are active in metastatic carcinoids. In a phase II study, we evaluated the effect upon diagnostic 131I-MIBG uptake and the clinical response of the combination. 131I-MIBG scintigraphy was performed prior to treatment, after 8 weeks of IFN and after unlabelled MIBG. The tumour over non-tumour (T/NT) ratios were quantitatively determined by comparing counts in the centre of the tumour (liver metastases) with those in an adjacent area of normal liver uptake (T/NT1) and with abdominal background area (T/NT2). The T/NT1 ratio showed an increase of >10% in only four out of 21 patients (19%) after IFN (P = 0.178) and significantly more often in nine out of 18 patients (50%) after unlabelled MIBG (P = 0.016). The absolute uptake in tumour deposits was also increased if compared with the abdominal background (T/NT2: 23% increase after IFN and 83% increase after unlabelled MIBG). The combination produced 91% of patients with stable disease (using World Health Organisation criteria) at computed tomography scan and a biochemical response (a reduction of at least 50% in urinary 5-hydroxyindolacetic acid excretion) in 39%. IFN-alpha did not significantly improve tumour retention of 131I-MIBG. In contrast, unlabelled MIBG significantly improved biodistribution and tumour uptake in 83%. A synergistic effect was not seen.

Lymphatic mapping with tracer administration into the primary breast cancer.

There is an ongoing debate over the best tracer injection technique in lymphatic mapping for breast cancer. The technique of low tracer volume administration into the primary breast cancer is presented. The reasons that led to this approach are explained as well as its advantages. Excision of radioactivity that remains at the injection site in the breast cancer prevents the gamma ray scatter that may hamper retrieval of a sentinel node. The intralesional injection technique avoids potential injection of tracer fluid across a lymphatic watershed, it enables identification of extra-axillary sentinel nodes and allows probe-guided excision of non-palpable tumours.

Impact of non-axillary sentinel node biopsy on staging and treatment of breast cancer patients.

The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of (99m)Tc-nanocolloid. The sentinel node was intraoperatively identified with the aid of intratumoural administered patent blue dye and a gamma-ray detection probe. Histopathological examination of sentinel nodes included step-sectioning at six levels and immunohistochemical staining. A sentinel node outside level I or II of the axilla was found in 149 patients (27%): internal mammary sentinel nodes in 86 patients, other non-axillary sentinel nodes in 44 and both internal mammary and other non-axillary sentinel nodes in nineteen patients. The intra-operative identification rate was 80%. Internal mammary metastases were found in seventeen patients and metastases in other non-axillary sentinel nodes in ten patients. Staging improved in 13% of patients with non-axillary sentinel lymph nodes and their treatment strategy was changed in 17%. A small proportion of clinically node negative breast cancer patients can be staged more precisely by biopsy of sentinel nodes outside level I and II of the axilla, resulting in additional decision criteria for postoperative regional or systemic therapy.

High sensitivity of radiolabelled antimyosin scintigraphy in assessing anthracycline related early myocyte damage preceding cardiac dysfunction.

In antimyosin scintigraphy was evaluated at various cumulative anthracycline dose levels in order to early identify patients with severe cardiac injury and increased long-term risk of cardiac dysfunction. Twenty-four patients receiving standard doses of 60-75 mg.m(-2) doxorubicin or 90-112.5 mg.m(-2) epirubicin were followed at baseline, low (two cycles), middle (four cycles), and high (six cycles) cumulative dose using (111)In antimyosin 48 h heart-to-lung ratio (HLR), left ventricle ejection fraction (LVEF) and peak filling rate (PFR). At a low cumulative dose only HLR was significantly increased (P=0.0001); at middle dose HLR (P<0.0001) and LVEF (P=0.0054), but not PFR, were significantly changed, and at high dose HLR (P<0.0001), LVEF (P=0.0001) and PFR (P=0.033) all changed significantly. Concerning individual results, HLR became abnormal in 18 patients (75%) at low, 22 (92%) at middle, and 24 (100%) at high cumulative dose whereas LVEF and PFR remained within normal limits in all patients. It is concluded that myocyte damage appears to precede left ventricle systolic and diastolic dysfunction in anthracycline treatment. (111)In antimyosin scintigraphy is very sensitive in detecting myocardial damage after cumulative dose levels even as low as 120-150 mg.m(-2) doxorubicin or 180-225 mg.m(-2) epirubicin.

The hidden sentinel node in breast cancer.

The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% (chi2, P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients.

[Therapeutic advances of nuclear medicine in oncology]. / Avances terapéuticos de medicina nuclear en Oncología.

With the development of new radiopharmaceuticals there is a tendency to apply nuclear medicine therapy for malignancies of higher incidence (lymphoma, prostate) than the ones which have been treated for many years (thyroid cancer, neuroendocrine tumours). One of the most important areas of current development in radionuclide cancer therapy is the monotherapeutic use of new or already available radiopharmaceuticals in preclinical or phase I studies and to a lesser degree in phase II trials. In this context, the radioimmunotherapy is showing important advances in the treatment of medullary thyroid carcinoma, malignant lymphomas en brain tumours with potential extension to neuroblastoma therapy. The development of DOTA as a chelating agent has lead to the use of Y-90-DOTATOC in the treatment of neuroendocrine tumours, particularly carcinoid tumours, and non-I131I-avid thyroid carcinomas. In an effort to improve tumour targeting together with simultaneous reduction of physiological organ uptake, 131I-MIBG is being used in combination with interferon a and pre-targeting with unlabelled MIBG in the treatment of carcinoid tumours. New routes of administration of radiopharmaceuticals (intratumoral, intra-arterial) have enhanced the treatment of malignancies of liver, pancreas and brain as well as the potential use of radioimmunotherapy by intravesical administration for bladder carcinoma. Another significant tendency in radionuclide therapy is its evolution from monotherapy towards a combined application with other anticancer modalities. Some recent examples of combined therapy with demonstrated anti-tumour effect are found in neuroblastoma (131I-MIBG and chemotherapy), bone metastases of prostatic carcinoma (addition of 89Sr to chemotherapy schedules), brain malignancies (adjuvant use of radioimmnunotherapy in relation to surgery and external radiotherapy) and lymphoma (radioimmunotherapy combined with chemotherapy or immunotherapy). Reinforcing this trend in phase II and III studies as well as the planning of multicenter trials following the guidelines and criteria of clinical oncology will determine the future advances in this field.

Improved sentinel node visualization in breast cancer by optimizing the colloid particle concentration and tracer dosage.

Faint lymph uptake may hamper sentinel node (SN) identification by scintigraphy and subsequent gamma probe localization. The aim of the present study was to evaluate an adjustment in the colloid particle concentration and tracer dosage to optimize mammary lymphoscintigraphy. Scintigraphy was performed in 151 patients with a palpable breast carcinoma and clinically negative axilla: for the first 75 patients (group A) a standard labelling of 0.5 mg nanocolloid with 99Tcm was performed, for the subsequent 76 patients (group B) the labelling dilution volume was reduced from 4 to 2 ml. For both groups the volume of injection was 0.2 ml. Lymph node uptake was evaluated by a 4-step visual score (from 0 = absent to 3+ = very intense), and by count quantification of at 4 h in the first draining SN. The SN visualization rate increased from 93% (70/75) in group A (mean dosage 93.4 MBq, range 57-130 MBq) to 99% (75/76) in group B (mean dosage 106.5 MBq, range 74-139 MBq). The percentage of patients with uptake 3+ was significantly higher (P = 0.001) in group B (51% vs 35% in group A). SN counts were significantly higher for group B (P<0.001). The percentage of patients with less than 2000 counts/node diminished from 45% in group A to 9% in group B (P = 0.001). In group B (P = 0.033) more lymph channels (53% vs 35% in group A) were visualized and for a longer time (26% vs 4% at 4 h). Axillary drainage was seen in 96% in group A and 98% in group B whereas non-axillary drainage was observed in 19% and 25%, respectively. Intraoperative SN identification rate was 97% in group A and 100% in group B. SN metastases were found in 41% of group A and 47% of group B. It is concluded that enhancement of colloid particle concentration and adjustment of tracer dosage led to improved SN identification by substantial increase in lymph node uptake and lymph vessel depiction. A significant reduction of cases with faint SN uptake enables better surgical efficacy.

Penile lymphoscintigraphy for sentinel node identification.

Lymphoscintigraphy for sentinel node (SN) identification has been extensively validated in breast cancer and melanoma. The aim of this study was to evaluate the findings of lymphoscintigraphy for SN identification in carcinoma of the penis. Lymphoscintigraphy was performed in 74 consecutive patients (mean age 62.2 years, range 28-87 years) with clinically lymph node-negative squamous cell carcinoma of the penis (stage T2 or greater). Following local anaesthesia by xylocaine 10% spray, technetium-99m nanocolloid (mean dose 64.8 MBq, range 40-131 MBq) in a volume of 0.3-0.4 ml was injected intradermally around the tumour. Shortly after injection, a 20-min dynamic study was performed with a dual-head gamma camera; subsequently, static anterior and lateral images were obtained at 30 min and 2 h using simultaneous cobalt-57 flood source transmission scanning. 57Co-assisted skin marking defined SN location for gamma probe/blue dye-guided biopsy, which was performed the next day. The SN visualization rate was 97% (72/74). Lymphatic drainage was bilateral in 81% of the cases (58/72), exclusively to the left groin in 13% (9/72) and only to the right groin in 6%. Bilateral lymph node drainage was synchronous in 38% (22/58) and asynchronous in 62% (in 18 patients the initial route was the left groin, and in the other 18, the right groin). Visualization before 30 min occurred in 66 patients (93%), in 64 of them (88%) already during the dynamic study. A total of 173 SNs were visualized (85 in the right groin, 88 in the left groin). Pitfalls were caused by inguinal skin contamination during injection (four patients) and intracavernous administration (one patient). At surgery, a total of 161 SNs were identified and removed. Sixteen patients (22%) had a tumour-positive SN and underwent standard regional lymph node dissection subsequently. During follow-up (median 28 months, range 3-74 months), two patients with a negative SN developed lymph node metastases in the mapped basin. It is concluded that penile lymphoscintigraphy is a valid and well-tolerated method for lymphatic mapping and SN identification. Although bilateral early inguinal drainage is the most frequent pattern, late imaging is recommended principally in patients with initial unilateral drainage in order to exclude delayed lymph node filling in the contralateral groin. SN identification may lead to a more accurate staging and avoid extensive lymph node dissection in the majority of patients with penile carcinoma.

Occult primary tumors of the head and neck: accuracy of thallium 201 single-photon emission computed tomography and computed tomography and/or magnetic resonance imaging.

OBJECTIVE: To determine the accuracy of thallium 201 single-photon emission computed tomography (thallium SPECT) and computed tomography and/or magnetic resonance imaging (CT/MRI) in the detection of occult primary tumors of the head and neck. DESIGN: Study of diagnostic tests. SETTING: National Cancer Institute, Amsterdam, the Netherlands. PATIENTS AND METHODS: Thirty-two patients with a neck node metastasis of an epithelial tumor and negative findings by mirror examination at initial presentation were included in the study. Twenty-nine patients underwent thallium SPECT and CT/MRI before examination under general anesthesia (EUA). In 3 patients only thallium SPECT was performed before EUA. Histological confirmation of an occult primary tumor during EUA was used as the gold standard. Negative radiodiagnostic and nuclear findings in the upper aerodigestive tract in the presence of a primary carcinoma other than of the head and neck were interpreted as true-negative findings. RESULTS: For thallium SPECT the following results were recorded: sensitivity, 67%; specificity, 69%; accuracy, 69%; positive predictive value, 33%; and negative predictive value, 90%. In 1 patient, thallium whole body scan indicated a primary carcinoma beyond the mucosal lining of the upper aerodigestive tract. The CT/MRI results were as follows: sensitivity, 71%; specificity, 73%; accuracy, 72%; positive predictive value, 45%; and negative predictive value, 89%. CONCLUSIONS: Thallium SPECT and CT/MRI showed comparable results for detection of occult primary tumors of the head and neck. A potential advantage of thallium SPECT is that it allows total body screening.

A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients.

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of 131I-MIBG (110 MBq) and with 131I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with 131I-chCE7, the subcutaneous tumours nearly disappeared; treatment with 131I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days with 131I-mAb chCE7 and of 24 days with 131I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by 131I-chCE7 compared with 131I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with 131I-MIBG and 131I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. 131I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not accumulate 131I-MIBG, and the antibody may hold potential for radioimmunotherapy, either by itself or in combination with 131I-MIBG.