Follow-up in neuroblastoma: comparison of metaiodobenzylguanidine and a chimeric anti-GD2 antibody for detection of tumor relapse and therapy response.

Early and correct diagnosis of local tumor recurrence, occurrence of metastases, and therapy response are essential in patients with neuroblastoma stage IV. The aim of the study was to evaluate the diagnostic value of metaiodobenzylguanidine (mIBG) and a chimeric GD2 antibody in the follow-up of patients with neuroblastoma. In a prospective study, mIBG (N = 31 scans) and immunoscintigraphy were compared with a chimeric antiganglioside antibody, ch14.18 (MAb) (N = 31 scans), labeled with technetium Tc 99m in the follow-up of 18 patients with stage IV neuroblastoma. The findings were compared with histologic findings, other imaging examinations, and clinical changes over the course of 4 to 6 years. For the diagnosis of local tumor recurrences, sensitivity was 80% for MAb and 70% for mIBG. Specificity was 93% for MAb and 72% for mIBG. The MAb was superior for the detection of skeletal metastases, with a sensitivity of 82% compared with 72% for mIBG. Specificity was 100% for both techniques. Also, for soft tissue/lymph node metastases, sensitivity for MAb was higher (50%) than for mIBG (31%). Specificity was 100% for each technique. In sequential studies, metastases were detected earlier with MAb (mean: 2.3 m for skeletal metastases, 3.6 m for soft tissue metastases) than with mIBG. After therapy, tumor uptake was visualized longer with mIBG (mean 6.3 m) than with MAb. The chimeric antibody ch14.18 is likely to be valuable for follow-up examinations and for assessment of therapy response because of earlier detection of new metastases.

Investigations on skeletal growth zones via bone scans as base of determination of optimal time for surgery in mandibular asymmetry.

UNLABELLED: AIM of the study was to find out wether there is a common stop of growth of mandibular bone, so that no individual determination of the optimal time for surgery in patients with asymmetric mandibular bone growth is needed. As there are no epiphyseal plates in the mandibular bone, stop of growth cannot be determined on X-ray films. METHODS: Bone scans of 731 patients [687 patients (324 male, 363 female) under 39 y for exact determination of end of growth and 44 (21 male, 23 female) patients over 40 y for evaluation of non-growth dependent differences in tracer uptake] were reviewed for the study. All the patients were examined 3 hours after injection of 99mTc-DPD. Tracer uptake was measured by region of interest technique in different points of the mandibular bone and in several epiphyseal plates of extremities. RESULTS: Tracer uptake in different epiphyseal plates of the extremities shows strong variation with age and good correlation with reported data of bone growth and closure of the epiphyseal plates. The relative maximum of bone activity is smaller in mandibular bone than in epiphyseal plates, which show well defined peaks, ending at 15-18 years in females and at 18-21 years in males. In contrast, mandibular bone shows no well defined end of growing but a gradually reduction of bone activity which remains higher than bone activity in epiphyseal plates over several years. CONCLUSION: No well defined end of growth of mandibular bone exists. The optimal age for surgery of asymmetric mandibular bone growth is not before the middle of the third decade of life, bone scans performed earlier for determination of bone growth can be omitted. Bone scans performed at the middle of the third decade of life help to optimize the time of surgical intervention.

Influence of patient position in myocardial SPECT on the diagnosis of CHD.

AIM: Of the study was to show that changing patient position from supine to prone results in improved specificity of myocardial SPECT (MS). METHODS: We examined the influence of patient position in MS on the diagnosis of coronary heart disease (CHD) in 151 patients. By using a Tc-99m-labeled compound (Tetrofosmin, Myoview, Nycomed, Amersham) examinations could be performed in supine and prone position within 35 minutes. Examinations were performed as a two-day stress-rest protocol with one gamma camera head and 180 degrees rotation without absorption correction. RESULTS: Semi-quantitative patient and heart phantom data show similar values for anterior and inferior wall in prone position in contrast to a lower count ratio of inferior to anterior wall in supine position. This demonstrates the importance of patient position with respect to artifacts specificity. Changing patient position from supine to prone mainly improves diagnostic specificity for CHD in the inferior wall in men (from 58% to 90%) and in the anterior wall in women (from 80% to 93%). Sensitivity is the same for both techniques. CONCLUSION: Changing patient position from supine to prone significantly improves diagnostic specificity while sensitivity remains unchanged.

Differential diagnosis of metastases in bone scans: chemotherapy induced bone necrosis.

AIM: Influenced by the incorrect diagnosis of a bone metastasis caused by bone necrosis we evaluated reasons and frequency of bone necrosis in patients referred for bone scanning in follow-up of tumors. METHODS: Bone scans performed within two years on patients with primary bone tumors or tumors metastatic to bone were reviewed in respect to the final diagnosis bone necrosis. RESULTS: We found the cases of three young patients who presented the appearance of hot spots on bone scintigrams which were finally diagnosed as bone necrosis. In two cases the diagnosis was based on histological findings, in one case the diagnosis was made evident by follow-up. All the three patients had been treated by chemotherapy and presented no other reason for the development of bone necrosis. Enhanced tracer uptake in all sites decreased within eight weeks up to two years without therapy. CONCLUSION: Single and multiple hot spots after chemotherapy may be originated by bone necrosis but mimicry metastases.

[Differential diagnosis of childhood osteomyelitis--classification according to scintigraphic, radiologic and magnetic resonance tomographic characteristics]. / Differentialdiagnostik der kindlichen osteomyelitis--Typisierung anhand szintigraphischer, radiologischer und magnetresonanztomographischer Charakteristika.

We present a retrospective study on children with the final diagnosis osteomyelitis, who have been examined in Tübingen from 1985 to 1991. The different types of infantile osteomyelitis were classified due to the causative organism and findings in 3-phase scintigraphy and X-ray films. For the chronic type of osteomyelitis the study was extended to the years from 1979 to 1991 and the results of an earlier report were included. We worked up 17 cases of acute/peracute osteomyelitis, including 5 cases of early infancy, 2 cases of tuberculosis, 2 Brodie's abscesses, 5 plasmacellular types, 2 cases of primary chronic multifocal osteomyelitis (PCMO), and 5 cases of unspecific chronic osteomyelitis. All cases were examined with scintigraphy, X-ray films and in part with magnetic resonance tomographic imaging. In 23 cases scintigrams and X-ray films were performed in the follow-up. We show the importance of scintigraphy for the early detection and localisation of osteomyelitis, the importance of findings on X-ray films for the specific diagnosis of osteomyelitis, and the importance of magnetic resonance tomography for high-resolution detection of the expansion of osteomyelitis.

Catecholamine secreting glomus tumor detected by iodine-123-MIBG scintigraphy.

We report the case of a 41-yr-old woman who presented with arterial hypertension and tinnitus in the right ear synchronous with pulse. She had previously undergone surgery for suspected pheochromocytoma without positive therapeutic effect. CT and MRI revealed a homogenous tumor with contrast enhancement in the right hypotympanon and foramen jugulare, and [123I]metaiodobenzylguanidine (MIBG) scintigraphy demonstrated strong tracer uptake in the same area. Selective venous sampling of catecholamines in the ipsilateral jugular vein confirmed the tumor to have originated from hormone production.

Experimental topographic study of high-resolution tympanocochlear scintigraphy using the human temporal bone model.

To determine the diagnostic value of tympanocochlear scintigraphy (TCS), which is still used for the visualization of alterations of labyrinthine bone metabolism due to active otosclerosis, resolution and detection limits were examined in a normal human temporal bone model. After incubation in technetium-99m-labeled diphosphonate solution, scintigraphic imaging showed the zygomatic process and the clivus as landmarks for fine structures of the petrous bone. For further differentiation, labyrinthine fine structures were marked with radioactive tracers of 0.5-1 mm2 each. High-resolution scintigraphic imaging gave two-point discrimination for structures as small as 2.5 mm apart. Localization of the activity patterns was improved by correlating imaging with X-ray photographs or by superimposition with masks of the prepared temporal bones drawn from the X-rays. The correlation of scintigraphic findings with X-ray photographs was found to provide a powerful method for improving the accuracy of localizing temporal bone metabolic changes as it is applicable clinically for studying the occurrence of small active otosclerotic foci.

A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma.

9 patients with stage IV neuroblastoma were treated with 19 courses of human/mouse chimeric monoclonal antiganglioside GD2 antibody ch14.18 at dose levels of 30, 40 and 50 mg/m2/day for 5 days per course. The maximum tolerated dose (MTD) per injection was 50 mg/m2/day. 7 patients received more than one course of treatment, and none revealed any human anti-mouse antibody (HAMA) response. Clinical side-effects of patients treated with ch14.18 were abdominal and joint pains, pruritus and urticaria. One patient presented with a transient pupillatonia, while 2 others showed a unilateral atrophy of the optical nerve that was probably attributable to prior therapies. A complete remission was seen in 2 patients, partial remission in 2 patients, a minor response in 1 patient and stable disease in 1 patient. 3 patients showed tumour progression. Thus, our results indicate that treatment with chimeric MAb ch14.18 can elicit some complete and partial tumour responses in neuroblastoma patients.

Incidental finding of a hepatic lesion: differential diagnostic problems for fibrolamellar hepatic carcinoma.

We report the case of a 39-yr-old female with a liver lesion that was incidentally detected by ultrasound. Examination of biopsy specimens revealed focal nodular hyperplasia. A metastatic tumor in the right os ilium developed in the following weeks and showed specific uptake of 99mTc-hepatic 2,6-dimethyliminodiacetic acid (HIDA), suggesting metastasis from a differentiated hepatocellular carcinoma. The final pathologic diagnosis was multifocal, solid and glandular hepatocellular carcinoma, partly differentiated as fibrolamellar carcinoma, and an osseous metastasis from the differentiated hepatocellular carcinoma.

[Follow-up evaluation of metastatic neuroblastoma using high dose [131I-meta]iodobenzylguanidine]. / Verlaufsbeurteilung des metastasierten Neuroblastoms mittels hochdosiertem [131J-meta]Jodobenzylguanidin.

Between 1989 and 1990 nine children with neuroblastoma stage IV (according to Evans) have been treated with high-dose [131I-meta]Iodobenzylguanidine (HD-mIBG). The total HD-mIBG dose administered to each child was at mean 699.3 +/- 111 MBq/kg body weight. Prior to (median 28 days) and after (median 50 days) HD-mIBG treatment a diagnostic scan with [123I-meta]Iodobenzylguanidine ([123I-m]IBG) was performed. Scans performed with HD-mIBG were superior to diagnostic scans for the detection of bone lesions in 8/9 children, for the detection of soft tissue lesions in 4/9 children, and for a more precise diagnosis of the primary tumor in 1 child. In 4 children lesions which were primarily identified in the therapeutic scan could be further observed in posttherapeutical examinations.

Noninvasive procedures for diagnosis of renovascular hypertension in renal transplant recipients--a prospective analysis.

The purpose of this study was to clarify the selectivity and specificity of noninvasive procedures for diagnosis of clinically suspected posttransplant renovascular hypertension. We prospectively investigated 25 renal transplant recipients with arterial hypertension and clinically suspected stenosis of the graft artery (8 female and 17 male patients; ages 45 +/- 15 years). We performed a captopril test with 25 mg captopril (n = 25), renography with technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) before and after angiotensin-converting enzyme (ACE) inhibition with determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (n = 23) and color-coded duplex ultrasonography of the transplant kidney vessels (n = 24). Renal transplant artery stenosis (RTAS) was excluded by renal arteriography in 20 patients and by operative evaluation or clinical follow-up in 5 patients. We identified 4 patients with RTAS and renovascular hypertension. The noninvasive methods showed the following results (sensitivity/specificity): (1) captopril test: 75%/67%; (2) renography combined with ACE-inhibition: 75%/84%; and (3) color-coded duplex ultrasonography: 100%/75%. We conclude that in patients with clinical evidence of RTAS most noninvasive diagnostic procedures are not sufficiently accurate to exclude the diagnosis. Only color-coded duplex ultrasonography did not fail to detect all patients with RTAS and may act as a screening test. Intraarterial renal angiography remains the most reliable and as-yet indispensable diagnostic test for transplant recipients to rule out RTAS.

Case report 756: Chronic multifocal osteomyelitis.

We report the case of a young boy referred to our Department of Nuclear Medicine under the suspicion of a malignant tumor. The leading clinical symptoms were pain in the joints and loss of weight and vitality. Radiographic findings were suggestive of osteogenic sarcoma, but bone scans showed multiple increased tracer depositions along the cortex of femur and tibia, and in the lower and upper jaw. The enrichment pattern was not typical for metastases, but more probably demonstrated the multiple foci of osteomyelitis. This assumption was confirmed by the histological findings, which were diagnosed as primary chronic osteomyelitis. This rare pediatric bone disorder has been described by Giedion et al. The etiology of the disease is unknown, and therapy is discussed controversely in literature.

A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a.

Nine patients with neuroblastoma stage IV were treated with the murine monoclonal antibody 14.G2a, directed against disialoganglioside GD2. The antibody was injected daily for 5-10 days and the total applied dosage ranged between 100 mg/m2 and 400 mg/m2. The peak serum levels of mAb 14.G2a ranged from 28 micrograms/ml to 61 micrograms/ml. Pharmacokinetic data obtained in three patients indicated that the serum elimination of mAb 14.G2a fits a two-compartment model, with an alpha-half-time (t1/2 alpha) between 0.66 h and 1.98 h and a beta-half-time (t1/2 beta) between 30.13 h and 53.33 h. All patients presented with a human anti-(mouse IgG) antibody response either during or shortly after therapy. Eight patients showed a continuous decrease in complement component C4 during therapy, as well as an initial decrease in C3c and an initial increase in C3a, all suggesting an activation of the complement cascade. Side-effects consisted of allergic reactions like pruritus, exanthema, urticaria and of severe pain, predominantly located in the abdomen and lower extremities, which required the use of continuous intravenous morphine. Four patients additionally developed a transient hypertension and one patient experienced a transient nephrotic syndrome. Three patients were treated in an adjuvant setting and are not evaluable for tumor response. Of the remaining six patients, two had a complete remission, two showed a partial remission, and two patients did not respond to treatment.

Detection of infection in postoperative orthopedic patients with technetium-99m-labeled monoclonal antibodies against granulocytes.

A prospective study of 106 orthopedic patients was performed for the detection of infection in the early postoperative stage using 99mTc-labeled murine Mabs directed against epitopes on granulocytes. Accuracy was 81% in the hips (n = 26), 81% in the thigh (n = 21), 84% in the knee (n = 19), and 100% in the tibia (n = 27). The technique did not work well in the spine where false-negative results were observed in the three patients studied. One patient suffered transient swelling of the eyelids following injection. Optimal imaging results were obtained 2-6 hr postinjection.

Treatment of neuroblastoma with [131I]metaiodobenzylguanidine: long-term results in 25 patients.

From 1984 to 1990 we have treated altogether 25 children with [131I]metaiodobenzylguanidine (131I-MIBG) for a refractory, relapsed or metastasized neuroblastoma. Three children had stage III and 22 children had stage IV of the disease; at diagnosis their ages were between 4 months and 10 years. Children with stage III disease had at diagnosis a median age of 3.0 years and at treatment 3.8 years. After first-line chemotherapy 2 children had achieved a complete remission (CR), while in 1 child the tumor did not respond (NR) to the initial treatment. At the time of 131I-MIBG treatment 2 children had relapsed and in the other one no further response was achievable. The children were treated by a 13.5 +/- 12.9 mCi/kg BW per course with a mean total dose of 280.7 +/- 243.9 mCi. One child achieved CR by 131I-MIBG alone, while in 2 cases no measurable success was observed. All 3 children were treated additionally by surgery, chemotherapy and bone marrow transplantation (BMT). Two children have died but one is alive and in CR. The 22 children with stage IV disease were treated in two different study groups. In group A, 14 children were studied for side-effects and response to 131I-MIBG. All children were pretreated with standard chemotherapy. Five were treated in relapse, 5 in progression and 3 at a refractory state of the disease; only 1 child was in complete remission when being treated with 131I-MIBG. Group A patients were treated with a mean of 2.4 courses, with 10.3 mCi/kg BW for each course.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparative diagnosis of focal liver changes using computed tomographic and scintigraphic methods]. / Vergleichende Diagnostik fokaler Leberveränderungen mittels Computer-Tomographie und szintigraphischer Methoden.

The value of scintigraphic methods for the diagnosis of focal lesions of the liver (IDA, colloids, blood pool) in comparison to dynamic sequential computer tomography (CT) has been examined in this study. We found CT to be diagnostic in typical cases. For example, focal nodular hyperplasia is characterized by a rapid, strong increase and subsequent decrease after application of contrast medium (71%), whereas hemangiomas show a delayed density increase mostly at the rim (20%). In the event of deviations from the typical pattern, scintigraphic methods have to be applied which then often yield a specific diagnosis, especially in hemangiomas, focal nodular hyperplasia, and adenomas (71%). Ultrasound findings indicating the possible presence of hemangiomas or focal nodular hyperplasia should lead to scintigraphic studies prior to CT, not only for reasons of economy.

Application of the murine anti-Gd-2 antibody 14.Gd-2a for diagnosis and therapy of neuroblastoma.

We have tested the sialoganglioside monoclonal antibody Gd-2a for scintigraphic diagnostic and for immunotherapy in children with neuroblastoma stage IV. We could confirm tumor sites with Gd-2a scans in 1/2 children. Doses of 20-60 mg/m2 were administered daily for 5-10 days. 2/2 children with multiple tumor sites showed significant tumor regression. Four children, treated preventively, are still in clinical remission. One child showed tumor progression despite Gd-2a treatment. Adverse effects included itching, rashes, and pain.

Application of an anti-myosin antibody for scintigraphic differential-diagnosis of infantile tumors.

Immunoscans with the Fab-fragment of the monoclonal anti-myosin antibody R11D10 labeled with 111In showed significant uptake in rhabdomyosarcoma, rhabdoid tumor, and primitive neuroectodermal tumor. The diagnosis of an antimyosin positive or negative tumor with the aid of the immunoscan was superior to clinical findings in combination with ultrasound and CT, and to histological diagnosis in tumor biopsies. In addition chemotherapeutically induced renal impairment can be diagnosed by diminished renal uptake of antimyosin.