Monte Carlo simulation of electron dose from (131)I-targeted tumor cells within a heterogeneous tumor.

BACKGROUND AND AIM: In internal radiotherapy, the variable distribution of target receptors within the tumoral tissue, and the variable ranges of electrons may be responsible for a heterogeneous dose distribution at the cellular level. The aim of the present study was to use Monte Carlo simulations to assess (131)I electron dose in a model of heterogeneous tumor containing multiple clusters of cancer cells, targeted by (131)I-labeled molecules. METHODS: The model consisted of 150-µm-diameter spherical tumor cell clusters, in which (131)I was homogeneously distributed. Clusters were placed 24 µm apart, separated by septa of nonradioactive connective tissue. The electron dose distribution to tumor cells in a single cluster was first assessed. Then was assessed the dose increase to these targets after adding multiple layers of neighboring clusters (total number of clusters = 15,624). RESULTS: Dose distribution within a single isolated cluster follows a decreasing gradient, the dose for the outermost cell layer being about half that at the center. When radioactive neighbors were added, the dose to the central cluster increased. The most important contribution was given by the nearest neighbors, whereas the contribution from neighbors beyond a distance of 1 mm was only for 5% of the final dose. If the central cluster was unlabeled, the absorbed dose to the outermost cell layer of this cluster was reduced by 27%, and that at the center by 45%. CONCLUSIONS: The electron cross-dose of (131)I falls rapidly as a function of distance and becomes negligible after just 1 mm. Small clusters of tumor cells that are not radiolabeled may receive a very small dose. Therefore, in internal radiotherapy it is important to aim at targeting tumor cells as homogeneously as possible, rather than relying on the cross-dose to achieve a therapeutic effect.

The sentinel node procedure in breast cancer: nuclear medicine as the starting point.

Axillary node status is a major prognostic factor in early breast cancer. Staging with sentinel node biopsy (SNB) leads to a substantial reduction in surgical morbidity. Recent multiinstitutional studies revealed SNB false-negative rates ranging from 5.5% to 16.7%, higher than the target (<5%) set by the 2005 guidelines of the American Society of Clinical Oncology. These alarming data point to the necessity of optimization. Dual mapping with radiotracer and blue dye, combining 2 different injection sites, and routinely using lymphoscintigraphy may improve accuracy. Factors associated with decreased sensitivity, such as prior excisional biopsy or neoadjuvant chemotherapy, should be recognized. The use of SNB in situations with a high prevalence of node positivity (large tumor, multifocality) is controversial. The risk of missed disease after negative SNB ranges from 1% to 4% in patients with T1 tumor and up to 15% in patients with T3. With peritumoral injection, internal mammary drainage is seen in about 20% of cases. Patients combining internal mammary drainage with a positive axillary sentinel node have close to a 50% probability of internal mammary involvement. Lymphoscintigraphy might thus be helpful in selecting patients for whom internal mammary radiation has a high benefit-to-risk ratio.

Nuclear Medicine in Early-Stage Melanoma: Sentinel Node Biopsy-FDG-PET/CT.

Sentinel node status is the most powerful prognostic factor in patients with early-stage melanoma. This review discusses several issues of clinical interest and technical points for an optimized sentinel node biopsy (SNB) procedure. The role of fluorodeoxyglucose positron emission tomography/computed tomography is clearly established in patients with suspicion of locoregional or distant recurrence of melanoma before any surgical decision. However, its role at initial staging or follow-up of patients with localized disease or with positive SNB is less clear. Further research and efforts should focus on identifying which groups of patients are at specific high risk of early distant recurrence.

Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer.

PURPOSE: The aim of this study was to determine the impact of the main clinicopathological and biological prognostic factors of breast cancer on (18)F-fluorodeoxyglucose (FDG) uptake. Only women with tumours larger than 20 mm (T2-T4) were included in order to minimize bias of partial volume effect. METHODS: In this prospective study, 132 consecutive women received FDG PET/CT imaging before starting neoadjuvant chemotherapy. Maximum standardized uptake values (SUV(max)) were compared to tumour characteristics as assessed on core biopsy. RESULTS: There was no influence of T and N stage on SUV. Invasive ductal carcinoma showed higher SUV than lobular carcinoma. However, the highest uptake was found for metaplastic tumours, representing 5% of patients in this series. Several biological features usually considered as bad prognostic factors were associated with an increase in FDG uptake: the median of SUV(max) was 9.7 for grade 3 tumours vs 4.8 for the lower grades (p < 0.0001); negativity for oestrogen receptors (ER) was associated with higher SUV (ER+ SUV = 5.5; ER- SUV = 7.6; p = 0.003); triple-negative tumours (oestrogen and progesterone receptor negative, no overexpression of c-erbB-2) had an SUV of 9.2 vs 5.8 for all others (p = 0005); p53 mutated tumours also had significantly higher SUV (7.8 vs 5.0; p < 0.0001). Overexpression of c-erbB-2 had no effect on the SUV value. CONCLUSION: Knowledge of the factors influencing uptake is important when interpreting FDG PET/CT scans. Also, findings that FDG uptake is highest in those patients with poor prognostic features (high grade, hormone receptor negativity, triple negativity, metaplastic tumours) is helpful to determine who are the best candidates for baseline staging.

(18)F-FDG PET/CT bone/bone marrow findings in Hodgkin's lymphoma may circumvent the use of bone marrow trephine biopsy at diagnosis staging.

PURPOSE: Accurate staging of Hodgkin's lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow. (18)F-FDG PET/CT is now widely used for assessing response to therapy in HL and a baseline study is obtained to improve accuracy. The aim of this retrospective analysis was to assess whether routine BMB remains necessary with concomitant (18)F-FDG PET/CT. METHODS: Data from 83 patients (newly diagnosed HL) were reviewed. All patients had received contrast-enhanced CT, BMB and (18)F-FDG PET/CT. Results of BMB were not available at the time of (18)F-FDG PET/CT imaging. RESULTS: Seven patients had lymphomatous involvement on BMB. Four patients had bone involvement on conventional CT (two with negative BMB). All patients with bone marrow and/or bone lesions at conventional staging were also diagnosed on (18)F-FDG PET/CT scan. PET/CT depicted FDG-avid bone/bone marrow foci in nine additional patients. Four of them had only one or two foci, while the other had multiple foci. However, the iliac crest, site of the BMB, was not involved on (18)F-FDG PET/CT. Osteolytic/sclerotic lesions matching FDG-avid foci were visible on the CT part of PET/CT in three patients. MRI ordered in three other patients suggested bone marrow involvement. Interim and/or end-therapy (18)F-FDG PET/CT documented response of FDG-avid bone/bone marrow foci to chemotherapy in every patient. CONCLUSION: (18)F-FDG PET/CT highly improves sensitivity for diagnosis of bone/bone marrow lesions in HL compared to conventional staging.

Parathyroid scintigraphy findings in chronic kidney disease patients with recurrent hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTX), either subtotal or total with forearm autografting, is a well-established treatment for refractory renal hyperparathyroidism (RHPT). However, 20-30% of patients develop persistent or recurrent disease. Obtaining accurate localization before reoperation is difficult. PATIENTS AND METHODS: The study group comprised 21 consecutive adult patients (18 undergoing haemodialysis and 3 with a renal graft) imaged using (99m)Tc-sestamibi/(123)I subtraction scintigraphy. Of the 21 patients, 12 had undergone one previous PTX and the other 9 between two and four parathyroid operations. All patients had symptoms and signs of severe RHPT. The mean serum PTH level was 1,142 pg/ml. (99m)Tc-Sestamibi and (123)I images were recorded simultaneously. Imaging views comprised a planar view of the neck and mediastinum, followed by a magnified pinhole view over the thyroid bed area. If parathyroid ectopy was detected, SPECT or SPECT-CT was performed. The forearm was imaged in case of autograft. RESULTS: Parathyroid scintigraphy was negative in one patient and positive in the other 20 (sensitivity 95.2%). One patient had uptake corresponding to two unresected parathyroid glands. Recurrence at the site of the partially resected gland or autograft was seen in 11 patients. However, six of them had a second (99m)Tc-sestamibi focus corresponding to a supernumerary parathyroid gland. Seven other patients had a supernumerary parathyroid gland as the sole cause of relapse. Three of the supernumerary glands showed major ectopy (intrathyroidal, low mediastinal, undescended within the vagus nerve). One patient had parathyromatosis with multiple parathyroid nodules scattered over the left side of the neck. Reoperation was possible in 13 patients, with no false-positive findings. CONCLUSION: Many patients referred with the hypothesis of hyperplasia of a subtotally resected parathyroid gland or autograft were found to harbour a supernumerary parathyroid gland missed at the initial surgery.

Effect of variation in relaxation parameter value on LOR-RAMLA reconstruction of 18F-FDG PET studies.

PURPOSE: We tested the impact of different values of the relaxation parameter lambda (lambda) on contrast and noise in line-of-response row-action maximum likelihood algorithm (LOR-RAMLA) in 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) imaging. METHODS: Phantom studies were performed on a Gemini XL PET/CT scanner. The NEMA/IEC (National Electrical Manufacturers Association/International Electro technical Commission) torso phantom was used and acquisition data were reconstructed with lambda values ranging from 0.025 to 0.1. Quality of the reconstructed images was evaluated by contrast recovery coefficients and background variability values according to the NEMA NU 2-2001 procedures. RESULTS: Contrast recovery coefficients and background variability increased significantly when lambda increased. The best noise-versus-resolution trade-off was obtained with lambda in the 0.04-0.06 range. For LOR-RAMLA reconstruction, the manufacturer allows a possible lambda choice from 0.025 to 0.1. We would not advise too small (0.025) or too large (0.1) lambda values which result in too smooth or too noisy images. CONCLUSION: We determined optimal lambda values in LOR-RAMLA on a Gemini XL PET/CT scanner. Caution is needed when using lambda values out of that range.

18F-FDG PET/CT imaging for an early assessment of response to sunitinib in metastatic renal carcinoma: preliminary study.

PURPOSE: Sunitinib is a new standard for the treatment of metastatic renal-cell carcinoma (RCC). We evaluated the accuracy of 18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in assessing early response to this antiangiogenic drug, which cannot be obtained with conventional CT. PROCEDURES: Patients had an FDG-PET/CT at baseline and another one for follow-up at the end of the first cycle (at day 42). For each examination, all lesions were registered and the maximum standardized uptake value (SUV(max)) was measured. The metabolic response on PET at day 42 was assessed, using European Organization for Research and Treatment of Cancer criteria. Morphologic response on CT at day 84 (after two cycles), using Response Evaluation Criteria in Solid Tumors criteria, was used as the reference standard. The long-term outcome was assessed by the progression-free survival. RESULTS: Twelve (12) patients who completed at least two cycles of sunitinib were assessed. The SUV(max) for the lesions with the highest uptake ranged between 2.9 and 11.8 for the 12 patients (mean = 6.3). Early PET/CT findings, after one cycle of sunitinib, were consistent with later CT results in 9 patients of 11 assessable patients: 1 patient progressed on PET and CT, 7 patients had stable disease, and 1 had a partial response. The other 2 patients had a metabolic partial response on PET and stable disease on CT. However, 1 patient achieved a partial response later in follow-up, suggesting that metabolic early changes are an indication of sunitinib activity. CONCLUSION: FDG-PET/CT seems to be an interesting tool for the early evaluation of response to sunitinib in metastatic RCC. Larger studies are needed to confirm these preliminary results and establish a prognostic value for PET/CT.

Calculation of electron dose to target cells in a complex environment by Monte Carlo code "CELLDOSE".

BACKGROUND: We used the Monte Carlo code "CELLDOSE" to assess the dose received by specific target cells from electron emissions in a complex environment. (131)I in a simulated thyroid was used as a model. METHODS: Thyroid follicles were represented by 170 microm diameter spherical units made of a lumen of 150 microm diameter containing colloidal matter and a peripheral layer of 10 microm thick thyroid cells. Neighbouring follicles are 4 microm apart. (131)I was assumed to be homogeneously distributed in the lumen and absent in cells. We firstly assessed electron dose distribution in a single follicle. Then, we expanded the simulation by progressively adding neighbouring layers of follicles, so to reassess the electron dose to this single follicle implemented with the contribution of the added layers. RESULTS: Electron dose gradient around a point source showed that the (131)I electron dose is close to zero after 2,100 microm. Therefore, we studied all contributions to the central follicle deriving from follicles within 12 orders of neighbourhood (15,624 follicles surrounding the central follicle). The dose to colloid of the single follicle was twice as high as the dose to thyroid cells. Even when all neighbours were taken into account, the dose in the central follicle remained heterogeneous. For a 1-Gy average dose to tissue, the dose to colloidal matter was 1.168 Gy, the dose to thyroid cells was 0.982 Gy, and the dose to the inter-follicular tissue was 0.895 Gy. Analysis of the different contributions to thyroid cell dose showed that 17.3% of the dose derived from the colloidal matter of their own follicle, while the remaining 82.7% was delivered by the surrounding follicles. On the basis of these data, it is shown that when different follicles contain different concentrations of (131)I, the impact in terms of cell dose heterogeneity can be important. CONCLUSION: By means of (131)I in the thyroid as a theoretical model, we showed how a Monte Carlo code can be used to map electron dose deposit and build up the dose to target cells in a complex multi-source environment. This approach can be of considerable interest for comparing different radiopharmaceuticals as therapy agents in oncology.

Slow dynamic lymphoscintigraphy is not a reliable predictor of sentinel-node negativity in cutaneous melanoma.

We reviewed data from 160 consecutive patients (89 M/71 F; 53.5 [range, 9-88] years) who had under-gone lymphoscintigraphy and sentinel lymph node biopsy (SNB) in our hospital for histologically proven cutaneous malignant melanoma (CMM) (located on the upper limb: 33; lower limb: 57; trunk: 44; and head and neck: 26 patients), with a Breslow index > 1 mm and without clinical or radiologic evidence of metastatic spread. Colloidal (99m)Tc-rhenium sulfide (36-76 MBq) was injected intradermally in the four quadrants around the tumorectomy scar, followed by dynamic acquisition and static imaging. SN(s) were identified in 157 patients (overall identification rate, 98%). Fast (< 20 minutes), intermediate (20-30 minutes), or slow (> 30 minutes) lymphatic drainage was observed, respectively, in 122 (78%), 24 (15%), or 11 (7%) cases. Overall malignancy rate was 15%, respectively found in 19 (16%), 2 (8%), and 2 (18 %) patients with fast, intermediate, or slow drainage. No statistical difference between SN-positivity rates of patients with fast (19/122 = 16%) versus intermediate or slow drainage (4/35 = 11.4%) was observed (p = 0.69). Therefore, lymphoscintigraphic SN appearance time in CMM patients is unable both to predict SN metastasis and spare them from undergoing SN excision.

18F-fluorodeoxyglucose positron emission tomography/computed tomography in AIDS-related Burkitt lymphoma.

This study aims to describe 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings in patients with AIDS-related Burkitt lymphoma, at various times of treatment, and to define its utility for a better patient management. We retrospectively studied 13 consecutive HIV-positive patients with Burkitt lymphoma who underwent one or more PET/CT. In 5 of 5 patients imaged before treatment, PET/CT confirmed all involved sites detected at conventional work-up and demonstrated additional sites in 4 of 5 patients. Lymph node involvement, which is known to be uncommon in endemic or sporadic Burkitt lymphoma, was present in 54% of patients. Additionally, in 3 patients, Burkitt lymphoma was predominantly located in parotid lymph nodes, which is also an unusual finding. A negative scan was encountered in 3 of 10 patients imaged during treatment and in 1 of 4 patients imaged after treatment completion and was always associated with lasting complete remission. Presence of residual area of uptake was related to both favorable and unfavorable outcome whether performed during treatment (5/7 and 2/7, respectively) or after (1/3 and 2/3, respectively). Areas of increased uptake could be observed in lung (4 cases) or esophagus (3 cases), and were clinically related to pneumonia or esophagitis. We recommend PET/CT for accurate initial staging of patients with AIDS-related Burkitt lymphoma. PET/CT is also useful to monitor treatment response, as regression of initial disease can be early observed. Furthermore, PET/CT appears to have prognostic value, as a negative scan was always associated with a favorable outcome.

Plasma exchanges overcome persistent iodine overload to enable 131I ablation of differentiated thyroid carcinoma.

BACKGROUND: Amiodarone has a high iodine content that can induce persistent iodine excess and may prevent radioiodine (RI) treatment. PATIENT: A 55-year-old obese man had taken amiodarone (200 mg/d) for 3 years and stopped 2 years earlier. He underwent total thyroidectomy for papillary cancer with extrathyroidal extension and a metastatic central lymph node, requiring RI treatment. But iodine overload, with no other documented iodinated drug intake, was found (urinary iodine excretion = 472 microg/24 h; normal < 150 microg/24 h), and persisted 3 months later. Plasma exchanges (PE) were prescribed. INTERVENTIONS AND RESULTS: Eight PE over 4 weeks were needed to eliminate 39,295 nmol of iodine. Urinary iodine excretion and serum iodine concentrations, before PE and after eight sessions were, respectively: 230 and 84 nmol/mmol of creatinine, and 811 and 71 nmol/L, enabling RI treatment (4 GBq (131)I). Post-therapy whole-body scan revealed cervical uptake (0.48% of the total administered dose) corresponding to usual thyroid remnants. Ablation efficacy was confirmed 6 and 24 months later by cervical ultrasonography combined with an undetectable serum thyroglobulin level after recombinant human thyrotropin stimulation. CONCLUSIONS: When spontaneous iodine elimination is too slow to allow RI treatment of high-risk thyroid carcinoma within a reasonable time after thyroidectomy, PE are reliable and effective to overcome iodine overload.

Effect of (18)F-FDG PET/CT imaging in patients with clinical Stage II and III breast cancer.

PURPOSE: To investigate the potential effect of using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial assessment of patients with clinical Stage II or III breast cancer. METHODS AND MATERIALS: During 14 consecutive months, 39 patients (40 tumors) who presented with Stage II or III breast cancer on the basis of a routine extension assessment were prospectively included in this study. PET/CT was performed in addition to the initial assessment. RESULTS: In 3 cases, PET/CT showed extra-axillary lymph node involvement that had not been demonstrated with conventional techniques. Two of these patients had hypermetabolic lymph nodes in the subpectoral and infraclavicular regions, and the third had a hypermetabolic internal mammary node. PET/CT showed distant uptake in 4 women. Of these 4 women, 1 had pleural involvement and 3 had bone metastasis. Overall, of the 39 women, the PET/CT results modified the initial stage in 7 (18%). The modified staging altered the treatment plan for 5 patients (13%). It led to radiotherapy in 4 patients (bone metastasis, pleural lesion, subpectoral lymph nodes, and internal mammary nodes) and excision of, and radiotherapy to, the infraclavicular lymph nodes in 1 patient. CONCLUSIONS: PET/CT can provide information on extra-axillary lymph node involvement and can uncover occult distant metastases in a significant percentage of patients. Therefore, initial PET/CT could enable better treatment planning for patients with Stage II and III breast cancer.

[Therapeutic response evaluation by nuclear functional imaging]. / Evaluation de la réponse thérapeutique par imagerie fonctionnelle nucléaire.

Nuclear functional imaging is a reliable technique for the early evaluation of conventional cytotoxic and cytostatic agents. It also represents a major tool for the development and validation of anti-tumor targeted therapies.

Bone metastases of differentiated thyroid cancer: impact of early 131I-based detection on outcome.

Bone is the second most frequent target of distant metastases in patients with differentiated thyroid cancer, and such forms carry a very poor prognosis. The impact of (131)I therapy in this setting is controversial. We describe the diagnostic circumstances and outcome of patients with bone metastases recently managed in two institutions. Among 921 consecutive thyroid cancer patients who had total thyroidectomy and (131)I ablation between January 2000 and December 2004 and who were subsequently monitored, bone metastases had been diagnosed in 16 patients. In three cases, the bone metastases were non-functioning (negative (131)I uptake) . These patients were treated with surgery and radiotherapy but progressed rapidly. The other 13 patients had functioning (positive (131)I uptake) bone metastases. In five of them, thyroid cancer was revealed by signs of distant involvement (bone pain, n = 4; dyspnea, n = 1). The bone metastases progressed in these five patients, despite local therapy and multiple courses of (131)I. The bone metastases in the remaining eight patients were discovered on the post-surgery (131)I therapy scan. Complementary radiological studies were negative except in one patient in whom one of the metastases (a 5 mm lesion of the right humerus) was visible on magnetic resonance imaging (MRI). Six of these patients showed a good response to (131)I therapy, with (131)I uptake and Tg levels becoming undetectable or showing a sharp fall. One patient refused (131)I therapy; bone metastases became visible on MRI within 1 year and the Tg level rose tenfold. The disease progressed in one patient despite (131)I therapy. Post-surgical (131)I ablation can contribute to early detection of bone metastases at a time when the Tg level may be only moderately elevated, when other radiological studies are negative, and when the disease is potentially curable by (131)I therapy.

[Interests and perspectives of PET-CT for breast cancer: review of the literature]. / Intérêts et perspectives de la TEP-TDM en sénologie: revue de la littérature.

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a technique of functional imaging whose interest in oncology does not cease growing. This article summarizes the results of the technique in senology. For the initial evaluation of locally advanced breast cancer (extended primitive lesion, axillary lymph nodes...), the FDG-PET makes it possible to evaluate lymph nodes (in particular internal mammary nodes) and to seek remote metastases. The sensitivity of the examination appears nevertheless low for the secondary lesions of small size and for bone metastases of osteoblastic form, for which the performances of the bisphosphonates scintigraphy are higher. For the search of a loco-regional or remote recurrence, the performances of FDG-PET are very interesting, including in the event of normality of the biological assessment. The impact of FDG-PET on the therapeutic strategy is undeniable and seems estimated at least 20%. FDG-PET is not recommended for the characterization of a breast lesion. In addition to the small tumoral size, the causes of false negative are mostly represented by the lobular histological form, by the tumours with low proliferation, the tumours of low grade and the well differentiated lesions. The causes of false positive are mainly in relation with inflammatory and/or infectious phenomena. For similar reasons, FDG-PET cannot replace the anatomy-pathological analysis of the axillary nodes. To evaluate the effectiveness of a neo-adjuvant chemotherapy, FDG-PET seems to be a powerful examination. Nevertheless, the data of the literature appear insufficient to recommend it in current practice. It is the same way for the prognostic interest.