Maria Simons

A comparison of iodine-123 meta-iodobenzylguanidine scintigraphy and single bone marrow aspiration biopsy in the diagnosis and follow-up of 26 children with neuroblastoma

In staging neuroblastomas, the demonstration of tumoural invasion of the bone marrow is an important criterion with regard to the therapeutic prospects and the prognosis. Iliac crest aspiration sampling has been used routinely for the detection of bone marrow metastases in neuroblastoma. However, due to the limited character of the sampling, it sometimes leads to false-negative results. Another procedure which is used to determine the extent of neuroblastoma is metaiodobenzylguanidine (mIBG) scintigraphy. In order to establish the respective merits of both diagnostic techniques retrospectively, 148 iodine-123 mIBG scans of 26 children with neuroblastoma have been re-evaluated and compared with the results of routine bone marrow samples obtained within a 4-week period before or after scanning. Three types of mIBG uptake in the bone/bone marrow could be differentiated: (1) no visualization of the skeleton; (2) diffuse uptake in the skeleton with or without focally increased uptake, which indicates massive, diffuse bone marrow invasion by the tumour; and (3) focal tracer accumulation in one or several bones. No tracer uptake was observed in the skeleton in 91 scans. In 89 of the 91 the bone marrow biopsy was negative. Twenty-four scans showed diffuse skeletal uptake with or without foci. The bone marrow biopsies were negative for eight of those 24 scans. Hyperactive foci in one or more bones without diffuse tracer accumulation in the skeleton were detected in 33 scans. In only 7 of these 33 scans did bone marrow biopsy specimens from the iliac MDP crest contain neuroblastoma cells. Available technetium-99m methylene diphosphonate (MDP) whole-body scintigrams were also compared with the corresponding mIBG scans. Thirty-eight mIBG scans showed no visualization of the skeleton; 99mTc-MDP scintigrams were also normal. Seven patients with diffuse mIBG uptake in the skeleton appeared as normal on the 99mTc-MDP scans. Among 27 cases showing focal mIBG uptake in the skeleton with or without diffuse uptake, only I8 demonstrated a hot spot on the bone scintigram. The results of our study indicate that for the assessment of bone marrow infiltration by neuroblastoma, 1231-mIBG scintigraphy is more sensitive than the conventional cytological examination of bone marrow smears routinely obtained from the iliac crest, has a very high sensitivity in excluding bone marrow invasion, has a high specificity for detecting bone marrow invasion, appears to be able to detect early tumoural deposits in the bone marrow before osseous invasion occurs as shown on the MDP scans and is superior to 99mTc-MDP bone scan in detecting bone/bone marrow metastases of neuroblastoma. In patients with a positive mIBG scan in the skeleton, bone marrow biopsy will not yield additional information.

Activity of iodine-123 metaiodobenzylguanidine in childhood neuroblastoma: lack of relation to tumour differentiation in vivo.

Abstract. Neuroblastoma (NB) tumour cells have a remarkable tendency to differentiate spontaneously or under the influence of certain drugs. It is not clear whether metaiodobenzylguanidine (MIBG) uptake correlates with differentiation of NB cells. In 28 tumours of 26 patients, iodine-123 MIBG uptake in primary NBs was studied in relation to tumour differentiation, tumour size, cell density and degree of necrosis in subsequently resected specimens. Genetic features such as the presence of chromosomal aberrations (1p-deletion and MYCN amplification) and/or P-glycoprotein (mdr-1 gene product) were also evaluated in relation to MIBG uptake. A highly variable and unpredictable intensity of MIBG uptake was observed in primary as well as secondary resected tumours. This intensity did not relate to any of the above-mentioned factors except that there was a trend towards more intense uptake with increasing size of the tumour. We conclude from our observations that, in contrast to commonly held opinion, well-differentiated tumours do not a priori show a lower MIBG uptake in vivo, even when there are a low number of viable cells and a high degree of necrosis. The degree of differentiation or tumour viability and necrosis following longstanding chemotherapeutic treatment cannot be predicted by the MIBG scan findings. The observed MIBG uptake may be importantly influenced by factors other than those associated with cellular differentiation.

Differential renal function measured by 99Tcm-DTPA and 99Tcm-DMSA in a complete unilateral renal obstruction rat model.

We performed a prospective study to determine whether 99Tcm-DTPA differential renal function (DRF) in the case of acute obstruction in a unipapillary kidney rat model shows a similar pattern of results as 99Tcm-DMSA in a multipapillary kidney model, and to exclude recirculation or a block of tubular transport of DMSA which might explain the discrepancy reported by Kelleher et al. In 15 male and 4 female Wistar rats (weight 300-350 g), 99Tcm-DMSA renal uptake was measured 24 h before complete obstruction of the right ureter, which served as reference values. Twenty-four hours after obstruction, 99Tcm-DTPA (18.5 MBq) renography and 99Tcm-DMSA (111 MBq) non-depth-corrected renal uptake measurements were performed in the 15 male rats; in the 4 female rats, 740 MBq of 99Tcm-DMSA were injected and absolute, non-depth-corrected renal uptake measured at 24, 48 and 72 h. 99Tcm-DMSA DRF of the right kidney ranged from 48 to 55% (mu: 51%; sigma: 2%) before obstruction and from 14 to 35% (mu: 24%; sigma: 6%) after obstruction, whereas 99Tcm-DTPA DRF ranged from 16 to 30% (mu: 25%; sigma: 4%). No significant differences were found between DRF measured by 99Tcm-DMSA and 99Tcm-DTPA (P = 0.18), or between DRF of the obstructed kidney as measured by 99Tcm-DMSA at 24, 48 and 72 h (P > 0.2). Hypothetically, the discrepancy between our findings and those of Kelleher et al. may be due to intratubular pressure. In conclusion, the present findings and those of Kelleher et al. suggest the differences in DRF following complete unilateral renal obstruction, as determined by DTPA and DMSA, are probably species-specific. Furthermore, recirculation and block of tubular transport are unlikely to contribute significantly to differences in DRF as measured by the two radiopharmaceuticals.

Visualization of muscles involved in unilateral tremor using 13N-ammonia and positron emission tomography

Using positron emission computerized tomography (PCT), a high uptake of IV injected 13N-ammonia was observed in the muscles of the right forearm and leg of a patient with a rightsided static tremor. In some muscles the concentration of 13NH3 was 8.5 times higher than in the symmetrical normal limb. Confrontation of the clinical, neurological, and electromyographic findings with the results of the PCT proved that the muscles with the high uptake corresponded to the muscles responsible for the tremulous movements. There is strong evidence that the high uptake of 13NH3 was related to the increased blood flow produced by the continuous rhythmic exercise of the muscles involved in the tremor. To our knowledge a similar observation has not been described before. It is suggested that the combined use of suitable positron emitters and PCT might provide a valuable tool for the noninvasive study of perfusion of individual skeletal muscles.

whole-body Bone Scan Findings in X-linked Hypophosphatemia

X-linked hypophosphatemia, also called phosphate diabetes, is the most frequent form of inherited rickets in North American. In a series of 38 untreated adult X-linked hypophosphatemia patients, Hardy et al suggested that scintigraphic findings may be attributed solely to degenerative arthritis. However, the authors present a 31-year old, drug-free, X-linked hypophosphatemia patient, in whom bone scan findings were more compatible with osteomalacia and secondary degenerative arthritis, rather than with isolated degenerative arthritis. These findings are in agreement with the biochemical and histologic proof of active osteomalacia in untreated adult X-linked hypophosphatemia patients, provided by Reid et al. The first whole-body bone images of X-linked hypophosphatemia are presented.

Aseptic necrosis. A scintigraphic imitator of osseous involvement in Ga-67 avid lymphoma.

Based on the data by Armas et al, avascular necrosis, a not uncommon treatment-associated complication in patients with lymphoma, it should be easily distinguishable from osseous lymphomatous involvement in patients with Ga-67 avid lymphoma. In avascular necrosis, Ga-67 uptake will be either absent, decreased, or normal, whereas in lymphoma Ga-67 uptake will be increased. The authors present a patient with Hodgkins disease who had new foci of simultaneously increased Ga-67 and Tc-99m MDP uptake because of avascular necrosis as proven by biopsy and long-term follow-up. The authors hypothesize that a possible-explanation for the discrepancy between this patient report and the series by Armas et al may be that increased Ga-67 is a delayed phenomenon related to healing.

Age- and sex-related 99Tcm-DMSA renal uptake at 24 h in children with a normal scintigram

We performed a retrospective study to determine the age- and sex-related normal values of absolute 99Tcm-DMSA uptake at 24 h in children with normal kidneys. Of the 576 scintigrams performed between 1993 and 1996, 136 (272 kidneys) were classified as ‘normal’ by two independent observers on the basis of the presence of a smooth cortical outline, the absence of cortical loss, relative uptake in the range 45–55% and normal echographic parenchymal findings. The 136 scintigrams were divided into eight groups based on the childrens age: Group I, < 1 month (2 boys); Group II, 1–3 months (6 boys, 8 girls); Group III, 4–7 months (7 boys, 6 girls); Group IV, 8–12 months (8 boys, 8 girls); Group V, 13–24 months (14 boys, 4 girls); Group VI, 25–36 months (6 boys, 13 girls); Group VII, 37–120 months (13 boys, 19 girls); Group VIII, 121–180 months (8 boys, 10 girls). In contrast to the results of Morris et al. using absolute 99Tcm-DMSA uptake at 4–6 h, we found that combined left and right kidney uptake increased until age 8 months (Group I, 22.0 ± 6.7%; Group II, 45.9 ± 5.0%; Group III, 50.8 ± 5.0%; Group IV, 56.9 ± 8.5%; P = 0.019), after which it reached a plateau (Group V, 55.4 ± 7.3%; Group VI, 60.1 ± 7.8%; Group VII, 62.0 ± 5.0%; Group VIII, 62.4 ± 6.3%). Uptake at 24 h tended to be lower in the girls than in the boys, but this difference was not significant.

Abnormal Tl-201 limb scan due to unilateral tremor.

An abnormal intra- and interextremity distribution pattern of TI-201 was observed on the limb scan of a patient with a unilateral tremor. This is ascribed to the increased blood flow in the muscles responsible for the tremor. The suggestion is made that the existence of tremor should be considered as a possible explanation for unexpected abnormalities on TI-201 limb scintigrams.