Whole Body Scanning in Medicine: II. Clinical Aspects

Various kinds of scans were performed on 439 patients, using several types of radioactive substances. Using I¹³¹, functioning metastases were demonstrated in 11 of 26 patients with follicular or papillary thyroid cancer; in three of these patients the results of scans were a decisive influence in attempting radioiodine therapy. Radioiron scans demonstrated extramedullary hematopoiesis in patients with polycythemia vera, myelofibrosis, and myelophthisic anemia. Radiocopper studies showed abnormal concentration in the kidneys in two patients with Wilson''s disease. Radioactive strontium localized in bone metastases in at least four patients with malignant disease. Liver and kidney scans, using I¹³¹-Rose Bengal and Hg²⁰³-Neohydrin respectively, have been useful in the management of patients suffering from malignant disease, renal hypertension, and certain other disorders.     

Effect of calcium levels on redistribution of Sr85 in bush bean plants

Summary When bush bean plants previously exposed to Sr⁸⁵ were transferred to solutions containing different levels of calcium without further addition of Sr⁸⁵, and calcium had relatively little, but some, effect on the redistribution of the Sr⁸⁵ in the plants. Calcium did tend to restrict movement of strontium. Sr⁸⁵ tended to concentrate in stems or old leaves, usually more so than calcium. New leaves particularly had lower Sr/Ca ratios than other plant parts indicating some discrimination in favor of calcium.     

Review of a 5-Year Experience with the Radiostrontium Bone Scintiscan

Radiostrontium (⁸⁵Sr) skeletal scintiscanning was done on 640 cases and 520 were included in a review. Forty-eight percent of 359 patients with biopsy-proved malignant disease had secondary skeletal involvement; in 17 percent the involvement was identified by scintiscanning alone. False-negative scintiscans were recorded in 0.9 percent. Unusual ⁸⁵Sr localization was found in a bone infarct, in proteus bursitis and in a pulmonary aspergillosis infiltrate. Serum alkaline phosphatase levels were found to be of little value in the evaluation for osseous metastasis, and normal acid phosphatase values in patients with prostatic carcinoma did not exclude the possibility of spread to the skeleton. Both the scintiscan and roentgenograms are essential in the evaluation of patients for metastatic bone disease.     

Radioisotopic Bone Scintigraphy with the Gamma Camera in the Investigation of Prostatic Cancer

Experience with x-rays, strontium-87m scintigraphy, and technetium-99m polyphosphate scintigraphy in the identification of bone metastases in 201 patients with prostatic cancer is reviewed. About 40% of the patients had demonstrable metastases in bone at the time of first presentation.Comparative studies of 247 x-ray and ^87mSr surveys indicated that x-rays failed to detect metastases in 10% of cases where they were identified by ^87mSr but that the isotopic survey similarly failed to detect radiologically evident deposits in 7% of cases.Similar studies comparing ^99mTc polyphosphate surveys with x-ray scans showed that x-rays missed isotopically detected metastases in 12% of cases, but in only one survey out of 67 did the isotope miss radiologically evident deposits. In a series of 32 patients investigated by both isotopic techniques ^99mTc polyphosphate did not fail to detect any metastases and identified deposits in one patient in whom they were missed by ^87mSr scintigraphy. About 15% of both x-ray and ^87mSr surveys gave equivocal results, but only 3% (2 out of 67) of ^99mTc polyphosphate surveys were equivocal.We concluded that ^99mTc polyphosphate bone scintigraphy with the gamma camera was the most reliable of the techniques used for the identification of bone metastases in patients with carcinoma of the prostate. The results of scintigraphy with ^87mSr suggested that serial surveys may provide early evidence of hormone resistance in prostatic cancer.     

The exchange of Ca2+-receptive protein complex (troponin) in the myofibrils of fast and slow skeletal muscles

In order to compare the role of the Ca²⁺-receptive protein (troponin), in the characteristic myofibrillar contractile response of chicken fast and slow skeletal muscles, the troponin in both kinds of myofibrils were partially exchanged, under slightly acidic conditions. The Ca²⁺- or Sr²⁺-activation of the ATPase of fast (or slow) skeletal myofibrils hybridized with slow (or fast) skeletal troponin profiles were also investigated. The results indicated that the Ca²⁺- or Sr²⁺-affinity of the myofibrillar ATPase activity were related to the species of troponin. This procedure for replacing troponin in myofibrils under physiological conditions in thus considered to be useful for the study of the Ca²⁺-regulatory mechanism in myofibrillar contraction.     

Distribution Features of Skeletal Metastases: A Comparative Study between Pulmonary and Prostate Cancers

Bone scintigraphies are widely applied for detecting bone metastases. The aim of this study was to investigate distribution features of bone metastases in pulmonary and prostate cancers. Bone scintigraphies were performed in 460 patients with pulmonary cancer and 144 patients with prostate cancer. Patients were divided into three groups according to the total number of bone metastases: few bone metastases, moderate bone metastases, and extensive bone metastases. We compared the distribution of bone metastases in the two cancers, and analyzed the relationship between the distribution of metastatic lesions and their metastatic patterns. A total of 2279 and 2000 lesions of bone metastases were detected in 258 patients with pulmonary cancer and 102 patients with prostate cancer, respectively. In patients with few bone metastases, the distributions of metastatic lesions in the vertebrae (χ² = 16.0, P = 0.000) and thoracic bones (χ² = 20.7, P = 0.002) were significantly different between pulmonary and prostate cancers. In cases with moderate bone metastases, the distributions in the vertebrae (χ² = 6.6, P = 0.010), pelvis (χ² = 15.1 P = 0.000), and thoracic bones (χ² = 38.8, P = 0.000) were also significantly different between the two cancers. However, in patients with extensive bone metastases, the distributions were very similar. As the total number of bone metastases increased, their distribution in pulmonary cancer did not noticeably change, but the distribution in the vertebrae and thoracic bones of prostate cancer patients significantly changed. Accordingly, the distribution characteristics of bone metastases differed in pulmonary and prostate cancers, mainly in the early stages of metastasis.     

Multimodality Imaging to Predict Response to Systemic Treatment in Patients with Advanced Colorectal Cancer

Aim

Aim of this study was to investigate the potential of ¹⁸F-FDG PET, diffusion weighted imaging (DWI) and susceptibility-weighted (T2*) MRI to predict response to systemic treatment in patients with colorectal liver metastases. The predictive values of pretreatment measurements and of early changes one week after start of therapy, were evaluated.

Methods

Imaging was performed prior to and one week after start of first line chemotherapy in 39 patients with colorectal liver metastases. ¹⁸F-FDG PET scans were performed on a PET/CT scanner and DWI and T2* were performed on a 1.5T MR scanner. The maximum standardized uptake values (SUV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC) and T2* value were assessed in the same lesions. Up to 5 liver metastases per patient were analyzed. Outcome measures were progression free survival (PFS), overall survival (OS) and size response.

Results

Pretreatment, high SUV_max, high TLG, low ADC and high T2* were associated with a shorter OS. Low pretreatment ADC value was associated with shorter PFS. After 1 week a significant drop in SUV_max and rise in ADC were observed. The drop in SUV was correlated with the rise in ADC (r=-0.58, p=0.002). Neither change in ADC nor in SUV was predictive of PFS or OS. T2* did not significantly change after start of treatment.

Conclusion

Pretreatment SUV_max, TLG, ADC, and T2* values in colorectal liver metastases are predictive of patient outcome. Despite sensitivity of DWI and ¹⁸F-FDG PET for early treatment effects, change in these parameters was not predictive of long term outcome.     

Strontium induces murine keratinocyte differentiation in vitro in the presence of serum and calcium

Primary mouse keratinocytes in culture are induced to terminally differentiate by increasing extracellular Ca²⁺ concentrations (Ca_O) from 0.05 mM to ≥ 0.1 mM. The addition of Sr²⁺ (≥ 2.5 mM) to medium containing 0.05 mM Ca²⁺ induces focal stratification and terminal differentiation, which are similar to that found after increasing the Ca_O to 0.12 mM. Sr²⁺ in 0.05 mM Ca²⁺ medium induces the expression of the differentiation-specific keratins, keratin 1 (K1), keratin 10 (K10), and the granular cell marker, filaggrin, as determined by both immunoblotting and immunofluorescence. Sr²⁺ induces the expression of those differentiation markers in a dose dependent manner, with an optimal concentration of 5 mM. In the absence of Ca²⁺ in the medium, the Sr²⁺ effects are reduced, and Sr²⁺ is ineffective when both Ca²⁺ and serum are deleted from the medium. Sr²⁺ treatment increases the ratio of fluorescence intensity of the intracellular Ca²⁺ sensitive probe, fura-2, indicating an associated rise in the level of intracellular free Ca²⁺ and/or Sr²⁺. At doses sufficient to induce differentiation, Sr²⁺ also increases the level of inositol phosphates in primary keratinocytes within 30 min. The uptake curves of ⁸⁵Sr²⁺ by primary keratinocytes are similar to those of ⁴⁵Ca²⁺. At low concentrations, the initial uptake of both ⁴⁵Ca²⁺ and ⁸⁵Sr²⁺ reaches a plateau within 1 hr; at higher concentrations, the uptake of both ⁴⁵Ca²⁺ and ⁸⁵Sr²⁺ increases continuously for 12 hr. In keratinocytes pre-equilibrated with ⁴⁵Ca²⁺ in 0.05 mM Ca²⁺ medium, Sr²⁺ causes an increase of ⁴⁵Ca²⁺ uptake, which is dependent on the presence of serum. These results suggest that Sr²⁺ utilizes the same signalling pathway as Ca²⁺ to induce keratinocyte terminal differentiation and that Ca²⁺ may be required to exert these effects. © 1993 Wiley-Liss, Inc.     

Skeletal growth in school children: maturation and bone mass

Skeletal growth and development was evaluated in 322 white children (age 6 to 14) using three different methods: (1) ¹²⁵I photon absorptiometry, (2) compact bone measures on radiographs, and (3) Greulich-Pyle skeletal age from hand-wrist radiographs. Bone mineral content, measured by photon absorptiometry, increased at an incremental rate of about 8.5% each year. Skeletal age was a poor predictor of skeletal status, i.e., bone mineral content (14% error), and did not decrease the predictive error substantially more than did chronological age. Gross morphology (height and weight) was in fact a better predictor of bone mineral content than were skeletal age, chronological age, and radiographic morphometry. Skeletal age deviations were correlated with deviations in body size. A bone mineral index was devised which was independent of body size and this index was also independent of skeletal age. Skeletal age is imprecise (3 to 6 months error) and the range of variation in normal children (13 months) overlaps the maturational delay of the malnourished and diseased. The difficulties in using skeletal maturation are discussed and it is suggested that particular maturational indices be used which better indicate skeletal growth than does a composite skeletal age.     

Improved immunoscintigraphy by subcutaneous injection of 99mTc or 111In labelled F(ab′)2 fragments of an anti-melanoma monoclonal antibody

Technetium-99m and/or ¹¹¹In labelled F(ab′)₂ fragments of a melanoma associated MoAb 225.28S were injected i.v. in 80 patients affected by stage I to IV malignant melanoma. Seventy five percent of metastatic lesions already documented by other methods were detected by immunoscintigraphy, which was also capable of detecting a certain number of unknown metastases. However, we observed a lower percentage of positive scans in liver, lung and skin because of the poor tumour to background ratio. In some patients, subcutaneous (s.c.) injection allowed us to visualize documented metastases undetected by i.v. administration. An equal amount of non-specific F(ab′)₂ fragments (MoAb 4C4) injected s.c. as a negative control showed no positive scans. Clinical studies and Chromatographic patterns of patient serum samples suggest that the s.c. route of administration offers, with respect to the i.v. route, the advantage of reducing vascular background and aspecific accumulation in liver, probably because of retention of possible contaminants by the lymphatic system.     

Effects of K+-induced depolarization and purinergic receptor activation on elemental content in insulin-producing RINm5F-cells.

X-ray microanalysis was used to detect elemental changes in the insulin-producing tumor cell-line RINm5F. To improve discrimination between mobile ions and ions bound to macromolecules a new approach was employed, consisting of multivariate statistical analysis of correlations between the concentrations of Na, Mg, P, S, Cl, K, and Ca. RINm5F cells, cultured on Formvar-coated titanium grids, were stimulated with high K⁺ or ATP, that are both known to stimulate insulin release. The buffers used contained Ca²⁺ or one of the Ca²⁺-analogues Sr²⁺ and Ba²⁺, to represent Ca²⁺ uptake in response to stimulation. After stimulation the cells were shock-frozen and freeze-dried overnight. Incubation for 10-20 seconds in a Ca²⁺-containing buffer did not significantly affect elemental composition, whereas cellular Mg, P and K decreased in a Sr²⁺-containing buffer. Depolarization with high K⁺ concentration caused an increase in the cellular Na content, both in Ca²⁺- and Sr²⁺-containing buffers, but not in the buffer where Ca²⁺ had been replaced by Ba²⁺. X-ray microanalysis is useful for detection of elemental changes subsequent to stimulation of cultured cells. Moreover, multivariate statistical analysis strengthens the idea that stimulation of RINm5F cells causes redistribution of ions possibly due to changes in the state of binding of some elements to cellular proteins.     

Intérêt de la TEP/TDM au 18FDG dans les sous-types histologiques agressifs de cancers thyroïdiens (oncocytaire et peu différencié)

IntroductionThe objective of our study was to evaluate the performance of ¹⁸FDG PET/CT in aggressive histological subtypes of differentiated cancer of the thyroid and its therapeutic impact.MethodThirty-three patients (22 Hürthle cell carcinoma and 11 poorly differentiated carcinoma) who underwent FDG PET/CT were retrospectively included. Nine scans have been performed for initial staging, 16 for suspicion of recurrence (with 11 having a rising Tg), 3 for the reassessment of metastatic disease under systemic treatment and 30 systematically during follow-up. The results of PET/CT were confronted with histological data and follow-up results.ResultsThirteen out of 18 positive scans were confirmed (8 locoregional recurrences and 5 distant metastases). The majority of them were performed for a suspicion of recurrence (8) or for initial staging (2). The sensitivity, specificity, PPV, and NPV were respectively 81.2%, 88.1%, 72.2% and 92.5%. For Hürthle cell carcinoma and poorly differentiated carcinoma, the sensitivity and specificity were respectively 100% vs. 57% and 86% vs. 93%. Systematic PET scans were most of the time negative (26/30) and in accordance with histological and follow-up results. It was the same in case of scans performed for undetectable initial Tg (16/22). PET/CT modified patient management in 14% of the cases.ConclusionThis study confirms the good performances of ¹⁸FDG PET/CT for initial staging and in case of elevated Tg during the follow-up of aggressive histological subtypes of thyroid cancer. It does not seem relevant in the absence of a suspicion of recurrence or in the case of undetectable initial Tg.     

The role of extracellular ions in the pathogenesis of myonecrosis induced by a myotoxin isolated from Broad-Banded Copperhead (Agkistrodon contortrix laticinctus) venom

Pathalogical changes in murine skeletal muscle cells induced by ACL (Agkistrodon contortix laticinctus, Broad-Banded Copperhead) myotoxin in vivo were compared to pathological changes induced by an influx of Ca²⁺ and other ions into cut skeletal muscle cells in vitro in the absence of myotoxin. In vivo, ACL myotoxin induced a rapid myonecrosis characterized by densely clumped myofibrils in the cytoplasm. In vitro, this pathological change was not produced by incubating skeletal muscle cells in Ca²⁺ concentrations as high as 200 mM, whereas skeletal muscle cells incubated in concentrations of 150 mM and 300 mM NaCl contained densely clumped myofibrils similar in morphology to muscle cells damaged by ACL myotoxin in vivo. Treatments of 300 mM KCl did not produce densely clumped myofibrils in muscle cells. These results suggest that an influx of Na⁺, possibly through disrupted regions of sarcolemma, be may primarily responsible for the pathological changes, including clumped myofibrils, induced by ACL myotoxin in vivo. However, an influx of extracellular Ca²⁺ which has been proposed to produce densely clumped myofibrils in muscle cells damaged by other snake venom myotoxins, may not be responsible for this pathological change since extracellular Ca²⁺ concentrations much higher than physiological levels did not produce this change in skeletal muscle cells in vitro.     

Fluxes of Ca2+, Sr2+ and Mg2+ in synaptosomes.

Synaptosomes isolated from sheep brain cortex accumulate Ca²⁺, Sr²⁺ and Mg²⁺ when incubated in isosmotic sucrose media containing 5 mM of either of these cations. The maximal levels of cations retained per mg of protein are 100 nmol of Ca²⁺, 85 nmol of Mg²⁺ and 80 nmol of Sr²⁺. The loss of Ca²⁺ or Sr²⁺ from the preloaded synaptosomes is increased by monovalent cations in the following order: Na⁺> K⁺ > Li⁺> choline, whereas for the loss of Mg²⁺ this order is different: K⁺ > Na⁺ > Li ～ choline. The efflux of Ca²⁺ or Sr²⁺ induced by monovalent cations decreases as the temperature is lowered and it is nearly abolished at 0°C, whereas the efflux of Mg²⁺ is much less influenced by temperature. The results suggest that the mechanism of exchange of Ca²⁺ for Na⁺ in synaptosomes operates similarly for Sr²⁺, but not for Mg²⁺.     

Radioiodine therapy of thyroid disease

Ten “ideal” steps used at the University of Michigan to treat well-differentiated thyroid cancer are presented. Using this in 103 patients with well-differentiated thyroid carcinoma and metastases outside their neck, those that were freed of their disease after ¹³¹I therapy survived three times as long as those not cured of their disease. Patients successfully cured of their metastases showed better conformity to the “ideal” steps than the patients with residual metastases. Each of the most commonly asked questions about ¹³¹I treatment of thyroid carcinoma following surgical treatment are discussed.     

Active Calcium and Strontium Transport in Human Erythrocyte Ghosts

Both calcium and strontium could be transported actively from erythrocytes if adenosine triphosphate, guanosine triphosphate, or inosine triphosphate were included in the hypotonic medium used to infuse calcium or strontium into the cells. Acetyl phosphate and pyrophosphate were not energy sources for the transport of either ion. Neither calcium nor strontium transport was accompanied by magnesium exchange, and the addition of Mg⁺⁺ to the reaction medium in a final concentration of 3.0 mmoles/liter did not promote the transport of either ion. In the absence of nucleotide triphosphates, the addition of 1.5 mmoles/liter of Sr⁺⁺ to the reaction solution did not bring about active calcium transport and similarly 1.5 mmoles/liter of Ca⁺⁺ did not bring about active strontium transport. The inclusion of 1.5 mmoles/liter of Ca⁺⁺ or Sr⁺⁺ in the reaction medium did not interfere with the transport of the other ion when the erythrocytes were infused with adenosine triphosphate.     

Embolie pulmonaire de découverte fortuite en TEP/TDM au 18F-fluorodésoxyglucose avec injection de produit de contraste iodé réalisée dans un contexte oncologique : à propos de trois cas cliniques

We report three cases of incidentally detected pulmonary embolism in oncologic ¹⁸F-FDG PET/CT scans. These pulmonary embolisms, without significant uptake of ¹⁸F-FDG, would not have been depicted without the contribution of contrast enhanced CT scans on an integrated PET/CT system. These three cases are contradictory to already published data describing focal uptake of ¹⁸F-FDG corresponding to thrombi.     

Skeletal Scintigraphy

Skeletal scintigraphy, using phosphates or diphosphonates labeled with technetium 99m, is a sensitive method of detecting bone abnormalities. The most important and most frequent role of bone scanning is evaluating the skeletal areas in patients who have a primary cancer, especially a malignant condition that has a tendency to spread to bone areas. The bone scan is superior to bone radiographs in diagnosing these abnormalities; 15 percent to 25 percent of patients with breast, prostate or lung cancer, who have normal roentgenograms, also have abnormal scintigrams due to metastases. The majority of bone metastases appear as hot spots on the scan and are easily recognized. The incidence of abnormal bone scans in patients with early stages (I and II) of breast cancer varies from 6 percent to 26 percent, but almost invariably those patients with scan abnormalities have a poor prognosis and should be considered for additional therapies. Progression or regression of bony lesions can be defined through scanning, and abnormal areas can be identified for biopsy. The incidence of metastases in solitary scan lesions in patients with known primary tumors varies from 20 percent to 64 percent. Bone scintigraphy shows positive uptake in 95 percent of cases with acute osteomyelitis. Stress fractures and trauma suspected in battered babies can be diagnosed by scanning before there is radiological evidence. The procedure is free from acute or long-term side effects and, except in cases of very young patients, sedation is seldom necessary.Although the test is sensitive, it is not specific and therefore it is difficult to overemphasize the importance of clinical, radiographic, biochemical and scanning correlation in each patient.     

Localisation of malignant germ-cell tumours by external scanning after injection of radiolabelled anti-alpha-fetoprotein.

Sheep IgG antibody to alpha-fetoprotein was labelled with 131I and used to identify human germ-cell tumours by emission scanning. Eleven patients were studied after resection of their primary tumours. Ten had malignant teratoma and one an endodermal sinus tumour. All eight patients with raised serum alpha-fetoprotein concentrations had metastases apparent in the antibody scans. Of the remaining three patients with normal serum alpha-fetoprotein concentrations, two had positive scans. Three of the patients with positive results were scanned twice; the second scans were negative after treatment, when the alpha-fetoprotein concentrations had returned to normal. These result suggest that antibody scans are useful in the clinical management of patients with germ-cell tumours.