Diagnostic value of 99mTc-HMPAO-labeled leukocytes scintigraphy in suspicion of post-sternotomy mediastinitis relapse.

BACKGROUND: The diagnostic value of radiolabeled white blood cells (WBCs) scintigraphy in mediastinitis is well established, but data in the specific context of relapse are lacking. The present study aimed at evaluation of the diagnostic value of WBCs scintigraphy in suspicion of mediastinitis relapse after prior surgical revision. METHODS AND RESULTS: Multiple planar incidences of the chest were acquired 4 and 20 hours after injection of labeled WBC in 43 patients. In case of non-conclusive scintigraphy, a second scan was performed 2-3 weeks after the first one. The diagnosis of infection was based on positive bacteriological results; otherwise patients were followed up for at least 1 year. Out of 39 analyzable patients, 17 (44%) were diagnosed with mediastinitis relapse. After the first scan, 32 of 39 were correctly classified, 2 were false positive, and 5 were not conclusive. After completion of an additional scan in the latter 5 patients, 36 of 39 were correctly classified and 3 were false positive (100% sensitivity, 86% specificity, 85% positive predictive value, and 100% negative predictive value). CONCLUSIONS: In the specific context of suspicion of mediastinitis relapse, the optimal diagnostic value was achieved by repeating the scan when the first one was not conclusive. In this context, a negative WBC scintigraphy was able to rule out infection, with potential major impact on therapeutic management in patients with poor clinical status.

[Nuclear medicine procedures in paediatric patients]. / Apport des techniques de la médecine nucléaire en pédiatrie.

The paediatricians rely primarily scintigraphic examinations in two situations: when they need functional information to decide operation (measurement of separate function of each kidney for example) or when they want to know if a bone disease is involved, in front of a sudden onset of musculoskeletal disorder. Kidney and bone scan represent 85% of applications for examinations. Some scintigraphic examinations have an essential role in the therapeutic evaluation and staging of malignancies such as MIBG-123 scintigraphy in neuroblastoma and FDG-18F scintigraphy in lymphoma. This presentation would not be complete without mentioning some tests whose indications in children are different from adults like the lung scan that evaluates separate functions of both lungs in diseases such as lung malformations and thyroid scintigraphy performed in cases of congenital hypothyroidism to determine the mechanism of this disease. Finally, to locate a Meckel's diverticulum in front of a gastrointestinal bleeding. Because of its indications, pediatric nuclear medicine concerns a high proportion of very young children, and must take into account the specificities of this age.

223Ra-dichloride therapy of bone metastasis: optimization of SPECT images for quantification.

BACKGROUND: 223Ra imaging is crucial to evaluate the successfulness of the therapy of bone metastasis of castration-resistant prostate cancer (CRPC). The goals of this study were to establish a quantitative tomographic 223Ra imaging protocol with clinically achievable conditions, as well as to investigate its usefulness and limitations. We performed several experiments using the Infinia Hawkeye 4 gamma camera (GE) and physical phantoms in order to assess the optimal image acquisition and reconstruction parameters, such as the windows setting, as well as the iteration number and filter of the reconstruction algorithm. Then, based on the MIRD pamphlet 23, we used a NEMA phantom and an anthropomorphic TORSO® phantom to calibrate the gamma camera and investigate the accuracy of quantification. RESULTS: Experiences showed that the 85 keV ± 20%, 154 keV ± 10%, and 270 keV ± 10% energy windows are the most suitable for 223Ra imaging. The study with the NEMA phantom showed that the OSEM algorithm with 2 iterations, 10 subsets, and the Butterworth filter offered the best compromise between contrast and noise. Moreover, the calibration factors for different sphere sizes (26.5 ml, 11.5 ml, and 5.6 ml) were constant for 223Ra concentrations ranging between 6.5 and 22.8 kBq/ml. The values found are 73.7 cts/s/MBq, 43.8 cts/s/MBq, and 43.4 cts/s/MBq for 26.5 ml, 11.5 ml, and 5.6 ml sphere, respectively. For concentration lower than 6.5 kBq/ml, the calibration factors exhibited greater variability pointing out the limitations of SPECT/CT imaging for quantification. By the use of a TORSO® phantom, we simulated several tumors to normal tissue ratios as close as possible to clinical conditions. Using the calibration factors obtained with the NEMA phantom, for 223Ra concentrations higher than 8 kBq/ml, we were able to quantify the activity with an error inferior to 18.8% in a 5.6 ml lesion. CONCLUSIONS: Absolute quantitative 223Ra SPECT imaging appears feasible once the dimension of the target is determined. Further evaluation should be needed to apply the calibration factor-based quantitation to clinical 223Ra SPECT/CT imaging. This will open the possibility for patient-specific 223Ra treatment planning and therapeutic outcome prediction in patients.

Reproducibility of differential renal function measurement using technetium-99m-ethylenedicysteine dynamic renal scintigraphy: a French prospective multicentre study.

OBJECTIVE: Dynamic renal scintigraphy remains the gold standard for assessing differential renal function (DRF). Recently, technetium-99m-ethylenedicysteine (Tc-EC) was shown to be valuable and had similar quality images as technetium-99m-mercaptoacetyltriglycine (Tc-MAG3). However, its reproducibility has never been confirmed. The aim of this study was to perform the first evaluation of Tc-EC reproducibility for assessing DRF in children who were referred for hydronephrosis or urinary tract dilatation. PATIENTS AND METHODS: A total of 109 patients from three French nuclear medicine departments prospectively underwent dynamic renal scintigraphy with Tc-EC. DRF reproducibility was assessed by different pairs of raters using a multilevel design that integrated local and centralized predefined procedures. RESULTS: Both local and centralized procedures yielded near-excellent inter-rater agreements, with all of the intraclass correlation coefficient values over 0.998. Bland-Altman plots showed a systematic bias of less than 1%, with the corresponding limits of agreements not exceeding the 5% threshold cut-off value that corresponds to the clinical definition of acceptable limits for this purpose. Intrarater agreements were also good to excellent. CONCLUSION: This prospective multicentre study showed that Tc-EC is highly reproducible for assessing DRF in a standard paediatric population, thus validating its use as an alternative to Tc-MAG3 in this setting.

Congenital Hypothyroidism: Role of Nuclear Medicine.

Thyroid scintigraphy holds a key place in the etiologic workup of neonatal hypothyroidism. Routine screening for this disorder in maternity hospitals in industrialized countries, for nearly 40 years, has permitted early treatment and thereby helped to prevent its physical and mental complications. Neonatal hypothyroidism affects approximately 1 in 3000 births. The most common causes are abnormal thyroid gland development and defective hormone synthesis by an eutopic thyroid gland. The incidence of the latter has risen in recent years, for reasons that remain unclear. A thorough etiologic workup helps to determine the disease type. Current guidelines recommend thyroid imaging by means of ultrasound and scintigraphy. Ultrasound should be done by a practitioner trained to examine the cervical region of newborns, as the thyroid is very small and must be distinguished from the particular aspect of the "thyroid empty lodge." Ultrasound lacks sensitivity for detecting small ectopic glands but is the gold standard for measuring thyroid dimensions. Scintigraphy provides an etiologic diagnosis in most cases. The two isotopes used in this setting are technetium-99m and iodine-123. The latter isotope gives more contrast and allows the perchlorate discharge test to be performed to detect abnormal iodide organification in the neonate with an eutopic thyroid. If scintigraphy cannot be performed during the neonatal period, a postponed procedure can be achieved after 3 years of age. Close cooperation between the nuclear medicine physician and the pediatric endocrinologist is crucial for timely and optimized scintigraphy.

Secondary ion mass spectrometry as a tool for investigating radiopharmaceutical distribution at the cellular level: the example of I-BZA and (14)C-I-BZA.

UNLABELLED: Further development of nuclear medicine for imaging and internal radiotherapy demands a precise knowledge of the tissue and cellular distribution of radiopharmaceuticals. Ion microscopy (secondary ion mass spectrometry [SIMS]) may be particularly useful in this respect. We used SIMS to study the biodistribution of the melanoma-targeting molecule N-(2-diethylaminoethyl)-4-iodobenzamide (I-BZA), both in its native state and radiolabeled with (14)C. METHODS: C57BL6/J1/co mice bearing pulmonary colonies of B16 melanoma cells were injected with I-BZA or (14)C-I-BZA. Appropriate tissues were fixed and included in epoxy embedding resin for SIMS studies. The distribution of unlabeled I-BZA was studied by detecting its stable iodine atom ((127)I). (14)C-I-BZA distribution was studied by dual detection of (127)I and (14)C. The time course of I-BZA concentrations at sites of tissue fixation was studied by measuring the signal ratio of (14)C and the naturally occurring isotope (13)C. RESULTS: SIMS showed that I-BZA concentrated in the cytoplasm of tumoral melanocytes (melanoma cells) and in the cytoplasm of tumor-infiltrating macrophages (melanophages). I-BZA was also detected in the cytoplasm of normal melanocytes in the pigmented structures of skin and eye. Interpretation of I-BZA distribution by using electron micrographs of adjacent sections showed that the intracytoplasmic melanin-rich organelles (melanosomes) were responsible for I-BZA retention. The distributions of (127)I and (14)C after (14)C-I-BZA injection were identical, even when I-BZA was separately labeled with (14)C at 2 different positions, indicating the stability of the amide bond of I-BZA. The time course of the (14)C/(13)C ratio in the melanosomes of melanoma cells suggested a retention half-life of about 38 h. CONCLUSION: Contrary to previous suggestions that I-BZA fixes principally to sigma-1 membrane receptors, our results strongly indicate that I-BZA associates with intracytoplasmic melanin pigments. Early I-BZA accumulation, in both melanocytes and melanophages, suggests that this compound fixes to preformed melanin rather than being incorporated during de novo melanin synthesis. These quantitative and qualitative data obtained with I-BZA illustrate the excellent potential of SIMS for studying the biologic fate of radiopharmaceuticals.

Weak uptake of 123I-MIBG and 18F-FDOPA contrasting with high 18F-FDG uptake in stage I neuroblastoma.

Hypertension in a 6-year-old girl was the presenting sign of a stage I neuroblastoma. This tumor corresponded to a left adrenal gland mass. Hypertension resolved immediately after complete surgical resection of the tumor with an uneventful follow-up (24 months at the present time). Preoperative assessment by nuclear medicine techniques showed weak uptake of I-MIBG and F-FDOPA contrasting with high F-FDG uptake by the tumor.

Long-term efficacy of radionuclide therapy in patients with disseminated neuroendocrine tumors uncontrolled by conventional therapy.

UNLABELLED: Therapeutic options in patients with advanced-stage gastroenteropancreatic (GEP) neuroendocrine tumors are limited. We compared the efficacy of radionuclide therapy with 111In-pentetreotide and 131I-metaiodobenzylguanidine (MIBG) in 20 patients (group A) with the outcome of similar patients who could not be treated for nonmedical reasons (group B, n = 12). The intent was to treat all patients because of uncontrolled tumor disease (n = 21), contraindication to chemotherapy or surgery (n = 7), or uncontrolled and badly tolerated clinical symptoms (n = 4). METHODS: Group A patients received 3 monthly administrations of 3.7-7.4 GBq of 131I-MIBG (n = 5) or 7 GBq of 111In-pentetreotide (n = 15), according to the best tracer uptake. Clinical evaluation, biologic tests, and conventional imaging were performed at 3, 6, 12, 18, and 24 mo. Therapy was considered beneficial if clinical status improved, laboratory tests for secreting tumors improved by >20%, tumor progression was halted, the size of the most significant localization had decreased by >25%, and the dosage of analgesic and cold somatostatin therapy could be lowered. Pejorative events were defined as side effects due to therapy, relapse in clinical symptoms, tumor progression, tumor laboratory marker increase, and death. RESULTS: The overall survival rate at 3 mo was significantly higher in group A (P = 0.05). Radionuclide therapy was beneficial in 14 patients (73% of group A), with only 1 significant side effect. The average time before relapse was 16.1 +/- 7.8 mo. The overall Kaplan-Meier survival rate and cumulative progression-free and cumulative event-free survival rates during the first 15 mo were significantly higher in patients receiving radionuclide therapy (P = 0.019, P = 0.024, and P = 0.019, respectively). CONCLUSION: Radionuclide therapy is feasible and safe and significantly defers the occurrence of fatal and nonfatal events in patients clinically uncontrolled by conventional therapy.

Parathyroid gland radionuclide scanning--methods and indications.

The usefulness of preoperative radionuclide scanning of the parathyroid glands in patients with primary or secondary hyperparathyroidism was long controversial because available techniques were of limited diagnostic efficacy. Technetium-99m-labeled sestamibi (99Tc-sestamibi) is a new radiopharmaceutical agent easily detected by gamma cameras. The first parathyroid imaging studies done with 99Tc-sestamibi about 10 years ago used a double-phase technique to separate thyroid and parathyroid tissue. Although promising, this method was less than ideal, particularly in multiple gland primary hyperparathyroidism and in secondary hyperparathyroidism. For several years, we have been using subtraction between two images acquired simultaneously, one with 99Tc-sestamibi, which binds to thyroid and parathyroid tissue, and the other with 123-iodine, which binds only to thyroid tissue. The remarkable efficacy of this technique in both primary and secondary hyperparathyroidism invites a reappraisal of the place of radionuclide imaging as a preoperative localization procedure done to reduce the need for repeat surgery. The usefulness of this technique in selecting candidates for unilateral surgery among patients with primary hyperparathyroidism is discussed.

Three-dimensional personalized Monte Carlo dosimetry in 90Y resin microspheres therapy of hepatic metastases: nontumoral liver and lungs radiation protection considerations and treatment planning optimization.

UNLABELLED: In the last decades, selective internal radiation therapy (SIRT) has become a real alternative in the treatment of unresectable hepatic cancers. In practice, the activity prescription is limited by the irradiation of organs at risk (OAR), such as the lungs and nontumoral liver (NTL). Its clinical implementation is therefore highly dependent on dosimetry. In that context, a 3-dimensional personalized dosimetry technique--personalized Monte Carlo dosimetry (PMCD)-based on patient-specific data and Monte Carlo calculations was developed and evaluated retrospectively on clinical data. METHODS: The PMCD method was evaluated with data from technetium human albumin macroaggregates ((99m)Tc-MAA) evaluations of 10 patients treated for hepatic metastases. Region-of-interest outlines were drawn on CT images to create patient-specific voxel phantoms using the OEDIPE software. Normalized 3-dimensional matrices of cumulated activity were generated from (99m)Tc-SPECT data. Absorbed doses at the voxel scale were then obtained with the MCNPX Monte Carlo code. The maximum-injectable activity (MIA) for tolerance criteria based on either OAR mean absorbed doses (D(mean)) or OAR dose-volume histograms (DVHs) was determined using OEDIPE. Those MIAs were compared with the one recommended by the partition model (PM) with D(mean) tolerance criteria. Finally, OEDIPE was used to evaluate the absorbed doses delivered if those activities were injected to the patient and to generate the corresponding isodose curves and DVHs. RESULTS: The MIA recommended using D(mean) tolerance criteria is, in average, 27% higher with the PMCD method than with the PM. If tolerance criteria based on DVHs are used along with the PMCD, an increase of at least 40% of the MIA is conceivable, compared with the PM. For MIAs calculated with the PMCD, D(mean) delivered to tumoral liver (TL) ranged from 19.5 to 118 Gy for D(mean) tolerance criteria whereas they ranged from 26.6 to 918 Gy with DVH tolerance criteria. Thus, using the PMCD method, which accounts for fixation heterogeneities, higher doses can be delivered to TL. Finally, absorbed doses to the lungs are not the limiting criterion for activity prescription. However, D(mean) to the lungs can reach 15.0 Gy. CONCLUSION: Besides its feasibility and applicability in clinical routine, the interest for treatment optimization of a personalized Monte Carlo dosimetry in the context of SIRT was confirmed in this study.

Cat-scratch disease and bone scintigraphy.

Cat-scratch disease is a bacterial infection caused by Bartonella henselae. Bone involvement is rare. We describe the case of a 7-year-old boy with a systemic form of the disease. He presented with a 15-day history of fever, altered general condition, weight loss and cough, associated with back pain, and right-sided coxalgia. Bone scintigraphy with Tc-99m hydroxymethylene diphosphonate showed spinal involvement, the iliac crest, the right ankle, and the right first metatarsal. Magnetic resonance imaging confirmed these locations. He was positive for anti-Bartonella henselae. The fever regressed before treatment with rifampicin began, and he made a full recovery.

Functioning pulmonary metastases of thyroid cancer: does radioiodine influence the prognosis?

Functioning pulmonary metastases are the most common distant lesions of differentiated thyroid cancer. About 50% of patients with such metastases die within 10 years. The impact of iodine-131 therapy is controversial. In this study we examined: (1) the early diagnostic value of post-surgery (131)I ablation for lung invasion and (2) the survival of patients receiving periodic (131)I therapy. Between January 1970 and December 1995 we provided initial treatment for 509 patients with thyroid cancer. Most of them (74%) underwent total thyroidectomy and (131)I ablation. Functioning pulmonary metastases occurred in 20 patients. All these patients received periodic (131)I therapy for as long as (131)I uptake persisted. Additional therapy consisted of lung surgery in three patients and local treatment of bone lesions in four patients. Follow-up data were recorded up to December 2001. Functioning pulmonary metastases occurred late in one patient, and were visible on the post-surgery (131)I therapy scan in the other 19 patients. At diagnosis of lung invasion, 11 patients had negative chest X-ray findings, and serum thyroglobulin levels were not suggestive of metastatic disease in 56% of these cases. One of the 11 patients with negative chest X-ray findings died with a neck recurrence, two have persistent pulmonary (131)I uptake, and the other eight are in apparent remission after receiving an average cumulative (131)I activity of 338 mCi (12.51 GBq). The nine patients with positive chest X-ray findings received an average of 939 mCi (34.74 GBq); two of them died, five are continuing to receive therapy and two are in apparent remission. Overall survival at 10 years is 84%. The average follow-up of the 17 survivors is 12.7 years. These results suggest that patients with functioning pulmonary metastases, even in advanced stages, may survive for many years on (131)I therapy. Early diagnosis, during post-surgery (131)I scanning, of radiologically inapparent metastases is associated with a better prognosis.