Thyroid scintigraphy: establishing a clinically useful normal range for 99mTc pertechnetate uptake.

PURPOSE: This study aims to establish a normal range for the thyroid uptake derived from 99mTc pertechnetate scans. In particular, variations of uptake with TSH stimulation and other factors such as urinary iodine concentration are taken into account and compared with the calculation of a raw uptake value. METHODS: Clinical multicentric (center A, B and C) prospective study on 125 consecutive healthy patients undergoing thyroid scans for thyroid nodules. Normal functional thyroid status was assured by normal TSH, normal thyroid size, no thyroid antibodies and no symptoms of thyroid functional disorders. Calculations of raw Tc-uptake (uptake) and modified uptake values regarding current TSH value (uptakeTSH1), urinary iodine concentration (uptakeTSH1&uic), gland volume, age, smoking status, weight and tissue thickness ventral to the thyroid were performed. RESULTS: There is a positive correlation of thyroid uptake with TSH allowing for the calculation of a normalized uptake value (uptakeTSH1). The normal range for uptakeTSH1 compares favourable to that for raw uptake in that it yields a clear distinction from thyroid functional disorders. The additional normalization for urinary iodine concentration (uptakeTSH1&uic) may even improve the distinctive power whereas further normalizations such as for gland volume, age and others are not warranted by this study. The 95% CI of uptakeTSH1 for sites A, A&B, and A&B&C were 0.21%-2.06%, 0.22%-2.38% and 0.24%-2.40%. CONCLUSION: A normal range for the thyroid uptake can be established with respect to the current TSH stimulation. This normalization (uptakeTSH1) overcomes the drawback of raw uptake by yielding a clinically useful parameter with obviously high distinctive power against functional thyroid disorders.

Thyroid Imaging Reporting and Data Systems: Applicability of the "Taller than Wide" Criterium in Primary/Secondary Care Units and the Role of Thyroid Scintigraphy.

BACKGROUND: To examine the applicability of the "taller than wide" (ttw) criterium for risk assessment of thyroid nodules (TNs) in primary/secondary care units and the role of thyroid scintigraphy therein. METHODS: German bicenter study performed in a setting of primary/secondary care. Patient recruitment and analysis in center A was conducted in a prospective manner. In center B, patient data were retrieved from a database that was originally generated by prospective data collection. TNs were assessed by ultrasound and thyroid scans, mostly fine needle biopsy and occasionally surgery and others. In center A, only patients who presented for the first time were included. The inclusion criterion was any TN ≥ 10 mm that had at least the following two sonographic risk features: solidity and a ttw shape. In center B, consecutive patients who had at least ttw and hypofunctioning nodules ≥ 10 mm were retrieved from the above-mentioned database. The risk of malignancy was determined according to a mixed reference standard and compared with literature data. RESULTS: In center A, 223 patients with 259 TNs were included into the study. For further analysis, 200 nodules with a reference standard were available. The overall malignancy rate was 2.5% (upper limit of the 95% CI: 5.1%). After the exclusion of scintigraphically hyperfunctioning nodules, the malignancy rate increased slightly to 2.8% (upper limit of the 95% CI: 5.7%). Malignant nodules exhibited sonographic risk features additional to solidity and ttw shape more often than benign ones. In addition to the exclusion of hyperfunctioning nodules, when considering only nodules without additional US risk features, i.e., exclusively solid and ttw-nodules, the malignancy rate decreased to 0.9% (upper limit 95% CI: 3.7%). In center B, from 58 patients, 58 ttw and hypofunctioning TNs on thyroid scans with a reference standard were available. Malignant nodules from center B were always solid and hypoechoic. The overall malignancy rate of hypofunctioning and ttw nodules was 21%, with the lower limit of the 95% CI (one-sided) being 12%. CONCLUSIONS: In primary/secondary care units, the lowest TIRADS categories for indicating FNB, e.g., applying one out of five sonographic risk features, may not be appropriate owing to the much lower a priori malignancy risk in TNs compared to tertiary/quaternary care units. Even the combination of two sonographic risk features, "solidity" and "ttw", may only be appropriate in a limited fashion. In contrast, the preselection of TNs according to hypofunctioning findings on thyroid scans clearly warranted FNB, even when applying only one sonographic risk criterion ("ttw"). For this reason, thyroid scans in TNs may not only be indicated to rule out hyperfunctioning nodules from FNB but also to rule in hypofunctioning ones.

Correct and Incorrect Recommendations for or against Fine Needle Biopsies of Hypofunctioning Thyroid Nodules: Performance of Different Ultrasound-based Risk Stratification Systems.

PURPOSE: To evaluate the recommendations for or against fine needle biopsy (FNB) of hypofunctioning thyroid nodules (TNs) using of five different Ultrasound (US) -based risk stratification systems (RSSs). METHODS: German multicenter study with 563 TNs (≥ 10 mm) in 534 patients who underwent thyroid US and surgery. All TNs were evaluated with ACR TI-RADS, EU-TIRADS, ATA, K-TIRADS 2016 and modified K-TIRADS 2021. A correct recommendation was defined as: malignant TN with recommendation for FNB (appropriate) or benign TN without recommendation for FNB (avoided). An incorrect recommendation was defined as: malignant TN without recommendation for FNB (missed) or benign TN with recommendation for FNB (unnecessary). RESULTS: ACR TI-RADS demonstrated the highest rate of correct (42.3 %) and lowest rate of incorrect recommendations (57.7 %). The other RRSs showed similar results for correct (26.5 %-35.7 %) and incorrect (64.3 %-73.5 %) recommendations. ACR TI-RADS demonstrated the lowest rate of unnecessary (73.4 %) and the highest rate of appropriate (26.6 %) FNB recommendation. For other RSSs, the rates of unnecessary and appropriate FNB were between 75.2 %-77.1 % and 22.9 %-24.8 %. The lowest rate of missed FNB (14.7 %) and the highest rate of avoided FNB (85.3 %) was found for ACR TI-RADS. For the other RSSs, the rates of missed and avoided FNB were between 17.8 %-26.9 % and 73.1 %-82.2 %. When the size cutoff was disregarded, an increase of correct recommendations and a decrease of incorrect recommendations was observed for all RSSs. CONCLUSION: The RSSs vary in their ability to correctly recommend for or against FNB. An understanding of the impact of nodule size cutoffs seems necessary for the future of TIRADS.

Distribution of Functional Status of Thyroid Nodules and Malignancy Rates of Hyperfunctioning and Hypofunctioning Thyroid Nodules in Germany.

AIM: Thyroid scintigraphy enables the depiction of the functional status of thyroid nodules (TNs) with both, 99mTc-pertechnetate and 123Iodine. The functional status is relevant for diagnostic procedures for the differentiation of benign and malignant TNs. The aim of this study was to examine the current frequencies of hyper-, hypo- and isofunctioning TNs in Germany and to estimate the risk of malignancy with regard to functional status. METHODS: In 11 study centers, a minimum of 100 nodules per center were consecutively enrolled between July 2019 and April 2020. Inclusion criteria were: newly diagnosed nodule, nodule' size of 10 mm or more, thyroid scintigraphy. Exclusion criteria were: completely cystic TNs, patients with prior radioiodine therapy or thyroid surgery. The risk of malignancy was estimated for hyper- and hypofunctioning TNs. RESULTS: Overall, 849 patients (72 % women) with 1262 TNs were included. Patients' age ranged from 18 to 90 years. Most TNs were hypofunctioning (n=535, 42%) followed by isofunctioning TNs (n=488, 39%) and hyperfunctioning TNs (n=239, 19%). When only TNs with a maximum size of 2 cm or more were considered the rate of hyperfunctioning and hypofunctioning TNs increased (to 27% and 49%) while isofunctioning TNs decreased. Only one of all hyperfunctioning TNs was malignant. In hypofunctioning nodules, the malignancy rate was estimated at 10%. CONCLUSION: In Germany, the proportion of hyperfunctioning TNs is approximately 20% and increases in larger TNs to up to 27%. Due to the low risk of malignancy in hyperfunctioning TNs, no further procedures to rule out malignancy are necessary. The risk of malignancy of hypofunctioning TNs is significantly higher. Thus, a thyroid scintigraphy is a useful diagnostic tool in Germany.

Introducing a Pole Concept for Nodule Growth in the Thyroid Gland: Taller-than-Wide Shape, Frequency, Location and Risk of Malignancy of Thyroid Nodules in an Area with Iodine Deficiency.

Purpose: (i) To examine the criterion taller-than-wide (TTW) for the sonographic assessment of thyroid nodules in areas of iodine deficiency in terms of frequency, anatomical distribution within the thyroid gland and risk of malignancy. (ii) To develop a model for nodule growth in the thyroid gland. Methods: German multicenter study consisting of two parts. In the prospective part, thyroid nodules were sonographically measured in all three dimensions, location within the thyroid gland and contact to a protrusion-like formation (horn) in the dorsal position of thyroid gland was noted. In addition, further sonographic features such as the composition, echogenity, margins and calcifications were investigated. All nodules from the prospective part were assessed for malignancy as part of clinical routine at the decision of the treating physician adhering to institutionally based algorithms. In the retrospective part, only nodules with fine needle aspiration and/or histology were included. The risk of malignancy in TTW nodules was determined by correlating them with cyotological and histological results. Results: Prospective part: out of 441 consecutively evaluated thyroid nodules, 6 were found to be malignant (1.4%, 95% CI 0.6-2.7%). Among the 74 TTW nodules (17%), 1 was malignant (1%, 95% CI 0-4%). TTW nodules were more often located in the dorsal half of the thyroid than non-TTW nodules (factor 2.3, p = 0.01, 95% CI 2.1-2.5) and more often located in close proximity to a horn than non-TTW nodules (factor 3.0, p = 0.01, 95% CI 2.4-3.8). Retrospective part: out of 1315 histologically and/or cytologically confirmed thyroid nodules, 163 TTW nodules were retrieved and retrospectively analyzed. A TTW nodule was 1.7 times more often benign when it was dorsal (95% CI 1.1-2.5) and 2.5 times more often benign when it was associated with a horn (95% CI 1.2-5.3). The overall probability of malignancy for TTW nodules was 38% (95% CI 30-46%) in this highly preselected patient group. Conclusion: TTW nodules are common in iodine deficient areas. They are often located in the dorsal half of the thyroid gland and are frequently associated with a dorsal protrusion-like formation (horn) of the thyroid. Obviously, the shape of benign nodules follows distinct anatomical preconditions within the thyroid gland. The frequency of TTW nodules and their predominant benignity can be explained by a pole concept of goiter growth. The difference between the low malignancy risk of TTW nodules found on a prospective basis and the high risk found retrospectively may be the result of a positive preselection in the latter.

Probing the role of methyl methacrylate release from spacer materials in induced membrane bone healing.

In the induced membrane (IM) technique for bone reconstruction, a poly(methyl methacrylate) (PMMA) spacer is implanted to induce formation of a foreign body membrane around the defect site. Membrane development is essential for later bone grafting success, yet the mechanism by which the IM promotes bone regeneration remains unknown, as are the ways that spacer composition plays a role in the membrane's healing potential. This study investigated the impact of leached methyl methacrylate (MMA)-the major monomeric component of PMMA-on IM development. In vitro cell culture found that MMA elution did not impact endothelial cell or mesenchymal stem cell proliferation. For in vivo analysis, we advanced a streamlined rat femoral model to efficiently study the influence of spacer properties on IM characteristics. Comparison of membrane formation around polycaprolactone (PCL), MMA-eluting PCL (high-dose PCL-MMA and low-dose PCL-MMA), and surgical PMMA revealed robust membranes enveloped all groups after 4 weeks in vivo, with elevated expression of osteogenic bone morphogenetic protein-2 and angiogenic vascular endothelial growth factor compared with the surrounding muscle and bone tissues. Growth factor quantitation in IM tissue found no statistically significant difference between groups. New bone growth, vascularization, and CD163+ macrophage populations surrounding the polymer implants were also quantified; and blood vessel formation around high-dose PCL-MMA was found to be significantly decreased compared with PCL alone. To the best of our knowledge, these findings represent the first time that results have been obtained about the characteristics of membranes formed around PCL in the IM setting.

Diagnostic Performance of Kwak, EU, ACR, and Korean TIRADS as Well as ATA Guidelines for the Ultrasound Risk Stratification of Non-Autonomously Functioning Thyroid Nodules in a Region with Long History of Iodine Deficiency: A German Multicenter Trial.

Germany has a long history of insufficient iodine supply and thyroid nodules occur in over 30% of the adult population, the vast majority of which are benign. Non-invasive diagnostics remain challenging, and ultrasound-based risk stratification systems are essential for selecting lesions requiring further clarification. However, no recommendation can yet be made about which system performs the best for iodine deficiency areas. In a German multicenter approach, 1211 thyroid nodules from 849 consecutive patients with cytological or histopathological results were enrolled. Scintigraphically hyperfunctioning lesions were excluded. Ultrasound features were prospectively recorded, and the resulting classifications according to five risk stratification systems were retrospectively determined. Observations determined 1022 benign and 189 malignant lesions. The diagnostic accuracies were 0.79, 0.78, 0.70, 0.82, and 0.79 for Kwak Thyroid Imaging Reporting and Data System (Kwak-TIRADS), American College of Radiology (ACR) TI-RADS, European Thyroid Association (EU)-TIRADS, Korean-TIRADS, and American Thyroid Association (ATA) Guidelines, respectively. Receiver Operating Curves revealed Areas under the Curve of 0.803, 0.795, 0.800, 0.805, and 0.801, respectively. According to the ATA Guidelines, 135 thyroid nodules (11.1%) could not be classified. Kwak-TIRADS, ACR TI-RADS, and Korean-TIRADS outperformed EU-TIRADS and ATA Guidelines and therefore can be primarily recommended for non-autonomously functioning lesions in areas with a history of iodine deficiency.

Combining a Vascular Bundle and 3D Printed Scaffold with BMP-2 Improves Bone Repair and Angiogenesis.

Vascularization is currently considered the biggest challenge in bone tissue engineering due to necrosis in the center of large scaffolds. We established a new expendable vascular bundle model to vascularize a three-dimensional printed channeled scaffold with and without bone morphogenetic protein-2 (BMP-2) for improved healing of large segmental bone defects. Bone formation and angiogenesis in an 8 mm critical-sized bone defect in the rat femur were significantly promoted by inserting a bundle consisting of the superficial epigastric artery and vein into the central channel of a large porous polycaprolactone scaffold. Vessels were observed sprouting from the vascular bundle inserted in the central tunnel. Although the regenerated bone volume in the group receiving the scaffold and vascular bundle was similar to that of the healthy femur, the rate of union of the group was not satisfactory (25% at 8 weeks). BMP-2 delivery was found to promote not only bone formation but also angiogenesis in the critical-sized bone defects. Both insertion of the vascular bundle alone and BMP-2 loading alone induced comparable levels of angiogenesis and when used in combination, significantly greater vascular volume was observed. These findings suggest a promising new modality of treatment in large bone defects. Level of Evidence: Therapeutic level I. Impact statement Vascularization is currently the main challenge in bone tissue engineering. The combination of a vascular bundle and an osteoinductive three-dimensional printed graft significantly improved and accelerated bone regeneration and angiogenesis in critical-sized large bone defects, suggesting a promising new modality of treatment in large bone defects.

Regenerative Approaches for the Treatment of Large Bone Defects.

A variety of engineered materials have gained acceptance in orthopedic practice as substitutes for autologous bone grafts, although the regenerative efficacy of these engineered grafts is still limited compared with that of transplanted native tissues. For bone defects greater than 4-5 cm, however, common bone grafting procedures are insufficient and more complicated surgical interventions are required to repair and regenerate the damaged or missing bone. In this review, we describe current grafting materials and surgical techniques for the reconstruction of large bone defects, followed by tissue engineering (TE) efforts to develop improved therapies. Particular emphasis is placed on graft vascularization, because for both autologous bone and engineered alternatives, achieving adequate vascular development within the regenerating bone tissues remains a significant challenge in the context of large bone defects. To this end, TE and surgical strategies to induce development of a vasculature within bone grafts are discussed. Impact statement This review aims to present an accessible and thorough overview of current orthopedic surgical techniques as well as bone tissue engineering and vascularization strategies that might one day offer improvements to clinical therapies for the repair of large bone defects. We consider the lessons that clinical orthopedic reconstructive practices can contribute to the push toward engineered bone.

FDG-PET/CT for the early prediction of histopathological complete response to neoadjuvant chemotherapy in breast cancer patients: initial results.

BACKGROUND: Up to about one-quarter of patients treated with neoadjuvant chemotherapy do not adequately respond to the given treatment. By a differentiation between responders and non-responders ineffective toxic therapies can be prevented. PURPOSE: To retrospectively test if FDG-PET/CT is able to early differentiate between breast cancer lesions with pathological complete response (pCR) and lesions without pathological complete response (npCR) after two cycles of neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: In this retrospective study 26 breast cancer patients (mean age, 46.9 years ± 9.9 years) underwent a pre-therapeutic FDG-PET/CT scan and a subsequent FDG-PET/CT after the second cycle of NACT. Histopathology of resected specimen served as the reference standard. Maximum standardized uptake values (SUVmax) of cancer lesions before and after the second cycle of NACT were measured. Two evaluation algorithms were used: (a) pCR: Sinn Score 3 and 4, npCR: Sinn Score 0-2; (b) pCR: Sinn Score 4, npCR: Sinn Score 0-3. The absolute and relative decline of the SUVmax (ΔSUVmax, ΔSUVmax(%))was calculated. Differences of the SUVmax as well as of the SUVmax decline between pCR lesions and npCR lesions were tested for statistical significance P < 0.05. To identify the optimal cut-off value of ΔSUVmax(%) to differentiate between pCR lesions and npCR lesions a receiver-operating curve (ROC) analysis was performed. RESULTS: Using evaluation algorithm A the ΔSUVmax was 13.5 (pCR group) and 3.9 (npCR group) (P = 0.006); the ΔSUVmax(%) was 79% and 47%, respectively (P = 0.001). On ROC analysis an optimal cut-off ΔSUVmax(%) of 66% was found. Using evaluation algorithm B the ΔSUVmax was 17.5 (pCR group) and 4.9 (npCR group) (P = 0.013); the ΔSUVmax(%) was 89% and 51%, respectively (P = 0.003). On ROC analysis an optimal cut-off ΔSUVmax(%) of 88% was found. CONCLUSION: FDG-PET/CT may be able to early differentiate between pCR and npCR of primary breast cancer lesions after two cycles of NACT.

Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma using 124-iodine: predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and depend on modes of TSH stimulation and number of preceding radioiodine therapies.

OBJECTIVE: Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2 Gy is considered to be safe. In this study, changes in the blood cell count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using 124I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed. METHODS: 198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using 124I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12 month after RAIT. RESULTS: There was no high-grade bone marrow toxicity (i.e. ≥ grade 3) in patients receiving less than 2 Gy blood dose-independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman's correlation coefficient >-0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered 131I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08 Gy/GBq) than in patients with exogenous TSH stimulation (0.06 Gy/GBq) and in patients with no previous RAIT (0.08 Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07 Gy/GBq). CONCLUSIONS: The range of BDpA among DTC patients is rather wide. Our results suggest that lower blood doses can be expected when using exogenous TSH stimulation and blood doses are generally higher at first RAIT compared to subsequent RAITs. Thus, we advise to make blood dosimetry standard praxis prior to a high-activity RAIT.

Comparison of FDG-PET/CT and bone scintigraphy for detection of bone metastases in breast cancer.

BACKGROUND: Bone scintigraphy is the standard procedure for the detection of bone metastases in breast cancer patients. FDG-PET/CT has been reported to be a sensitive tool for tumor staging in different malignant diseases. However, its accuracy for the detection of bone metastases has not been compared to bone scintigraphy. PURPOSE: To compare whole-body FDG-PET/CT and bone scintigraphy for the detection of bone metastases on a lesion basis in breast cancer patients. MATERIAL AND METHODS: Twenty-nine consecutive women (mean age 58 years, range 35-78 years) with histologically proven breast cancer were assessed with bone scintigraphy and whole-body FDG-PET/CT. Twenty-one patients (72%) were suffering from primary breast cancer and eight patients (28%) were in aftercare with a history of advanced breast cancer. Both imaging procedures were assessed for bone metastases by a radiologist and a nuclear medicine physician. Concordant readings between bone scintigraphy and FDG-PET/CT were taken as true. Discordant readings were verified with additional MRI imaging in all patients and follow-up studies in most patients. RESULTS: A total of 132 lesions were detected on bone scintigraphy, FDG-PET/CT or both. According to the reference standard, 70/132 lesions (53%) were bone metastases, 59/132 lesions (45%) were benign, and three lesions (2%) remained unclear. The sensitivity of bone scintigraphy was 76% (53/70) compared to 96% (67/70) for FDG-PET/CT. The specificity of bone scintigraphy and FDG-PET/CT was 95% (56/59) and 92% (54/59), respectively. According to the reference standard bone metastases were present in eight out of the 29 patients (28%), whereas 20 patients (69%) were free of bone metastases. One (3%) patient had inconclusive readings on both modalities as well as on MRI and follow-up studies. Bone scintigraphy and FDG-PET/CT correctly identified seven out of eight patients with bone metastases and 20 out of 20 patients free of metastases. CONCLUSION: On a lesion-basis whole-body FDG-PET/CT is more sensitive and equally specific for the detection of bone metastases compared with bone scintigraphy.

Diagnosis and dosimetry in differentiated thyroid carcinoma using 124I PET: comparison of PET/MRI vs PET/CT of the neck.

PURPOSE: This study compares intrinsically coregistered 124I positron emission tomography (PET) and CT (PET/CT) and software coregistered 124I PET and MRI (PET/MRI) images for the diagnosis and dosimetry of thyroid remnant tissues and lymph node metastases in patients with differentiated thyroid carcinoma (DTC). METHODS: After thyroidectomy, 33 high-risk DTC patients (stage III or higher) received 124I PET/CT dosimetry prior to radioiodine therapy to estimate the absorbed dose to lesions and subsequently underwent a contrast-enhanced MRI examination of the neck. Images were evaluated by two experienced nuclear medicine physicians and two radiologists to identify the lesions and to categorize their presumable provenience, i.e. thyroid remnant tissue (TT), lymph node metastasis (LN) and inconclusive tissue. The categorization and dosimetry of lesions was initially performed with PET images alone (PET only). Subsequently lesions were reassessed including the CT and MRI data. RESULTS: The analyses were performed on a patient and on a lesion basis. Patient-based analyses showed that 26 of 33 (79%) patients had at least one lesion categorized as TT on PET only. Of these patients, 11 (42%) and 16 (62%) had a morphological correlate on CT and MRI, respectively, in at least one TT PET lesion. Twelve patients (36%) had at least one lesion classified as LN on PET only. Nine (75%) of these patients had a morphological correlate on both CT and MRI in at least one LN PET lesion. Ten patients (30%) showed at least one lesion on PET only classified as inconclusive. The classification was changed to a clear classification in two patients (two LN) by CT and in four (two TT, two LN) patients by MRI. Lesion-based analyses (n=105 PET positive lesions) resulted in categorization as TT in 61 cases (58%), 16 (26%) of which had a morphological correlate on CT and 33 (54%) on MRI. A total of 29 lesions (27%) were classified as LN on PET, 18 (62%) of which had a morphological correlate on CT and 24 (83%) on MRI. In 16 lesions (15%) PET alone allowed no definite categorization. Categorization was achieved with the aid of CT and MRI, respectively, in five (one TT, four LN) and in six (two TT, four LN) lesions. In direct comparison, 23 lesions were not discernible on CT but clearly visible on MRI, 15 of which were smaller than 10 mm and about two thirds were classified as TT. Redoing dosimetry based on the volume information from MRI for these small lesions would have changed the initial therapy regime in five patients. These patients would have received (131)I therapy with standardized activities of 3.7 GBq or 7.4 GBq instead of activities higher than 10 GBq and would have benefited from reduced radiation exposure. CONCLUSION: PET/MRI is superior to PET/CT in terms of tracing back a PET focus to a morphological correlate. For this reason PET/MRI enhances diagnostic certainty for lesions<10 mm and improves pretherapeutic lesion dosimetry in DTC.

Clinical applications of 124I-PET/CT in patients with differentiated thyroid cancer.

(124)I-PET/CT has a high clinical potential in patients with differentiated thyroid cancer (DTC). Two aspects deserve special mention: staging of recurrent or residual disease and pretherapy dosimetry. Used in combination (124)I-PET and CT allows foci of highly specific (124)I uptake to be localized with a low radiation dose, which is specifically important in pretherapy diagnostics. In addition in the combination of FDG-PET and CT non-iodine-avid lesions may be detected and may be discriminated from simultaneously occurring iodine-positive lesions. In clinical applications, the pretherapy (124)I-PET dosimetry may result in a significant alteration in the therapeutic procedure compared to standard therapy using fixed therapeutic activities. In this context, (124)I-PET dosimetry is a useful procedure especially in advanced DTC, and allows the administration of safer and more effective radioiodine activities as well as earlier multimodal interventions compared to standard empirical protocols. This review summarizes the clinical data on (124)I-PET/CT in patients with DTC, and addresses future prospects.

Time course of tumor SUV in 18F-FDG PET of breast cancer: presentation of a simple model using a single reference point for time corrections of tumor SUVs.

UNLABELLED: Tumor standardized uptake values (SUVs) vary with the interval between 18F-FDG injection and image acquisition. This paper presents a simple method using a single reference point to make appropriate time corrections for tumor SUVs. METHODS: The reference point method was algebraically deduced from observations made by Beaulieu et al., who found that tumor SUVs behaved linearly over time (∼30 to 75 min after 18F-FDG injection). Eighteen patients with breast cancer were dynamically examined with PET/CT (∼60 and 80 min after 18F-FDG injection). Maximum SUV was calculated by applying 2 different iterative reconstruction methods (high-definition reconstruction and attenuation-weighted ordered-subsets expectation maximization). Reference points for time corrections were given, and errors for corrections obtained with the reference point method were calculated. RESULTS: Variations in the reconstruction algorithm strongly influenced the coordinates of the reference point. Time corrections using the reference point method were more accurate at higher tumor SUVs (>8 at high-definition reconstruction and>6 at attenuation-weighted ordered-subsets expectation maximization) than at lower ones. CONCLUSION: A common origin of tumor SUVs over time exists in breast cancer. In combination with the linear behavior of tumor SUVs between approximately 30 and 80 min, such a reference point allows for straightforward time corrections of tumor SUVs. Parameters for image reconstruction must be considered because they influence the coordinates of the reference point.

Postoperative FDG-PET/CT staging in GIST: is there a benefit following R0 resection?

AIM: Resection of the primary tumor with intraoperative staging is the standard procedure in patients with gastrointestinal stromal tumors (GIST). FDG-PET/CT has shown high accuracy when assessing treatment response in GIST patients. This study was designed to assess the accuracy of postoperative FDG-PET/CT to stage for occult tumor seeding in patients with R0 resection and without intraoperative detection of metastases. PATIENTS AND METHODS: 48 consecutive patients (mean age: 59 y) with histologically proven GIST underwent whole-body FDG-PET/CT after R0-resection without intraoperative detection of metastases. Fused data sets were assessed for metastases by a nuclear medicine physician and a radiologist. Histology of potential lesions and a clinical/radiological follow-up with a mean of 614±415 d served as standards of reference. RESULTS: FDG-PET/CT detected occult peritoneal metastases in 2 patients (4%). In 6 patients (13%) who later developed metastases postoperative FDG-PET/CT was falsely negative. False-positive findings were detected in 5 cases (10%) caused by increased FDG-uptake due to tissue regeneration postoperatively. In 3 patients (6%) other, formerly unknown malignancies were detected. The sensitivity and specificity of FDG-PET/CT for the detection of intraoperatively occult GIST metastases were 25% and 88%, respectively. CONCLUSION: FDG-PET/CT performed immediately after R0-resection of GIST without intraoperative detection of metastases does not seem to be a sufficient tool to detect clinically occult metastases.

A purging procedure for pantoprazole and 4-lumen catheters to prevent IV drug incompatibilities.

OBJECTIVE OF THE STUDY: The purpose of this prospective intervention study was to assess the number of patients with Y-site incompatibilities before and after implementation of quality improvement measures to prevent incompatibilities consisting of a focused instruction for pantoprazole as a drug frequently involved in incompatible drug pairs and of a recommendation to use 4-lumen instead of 3-lumen catheters to increase the number of available central infusion lines. SETTING: Cardiovascular intensive care unit where several standard operating procedures (SOPs) dealing with compatibility were already in place. METHOD: In a prospective intervention study, patients' IV medication was assessed for potential incompatibilities using a database containing compatibility information on approximately 60,000 drug pairs. In a first period, routine administration was monitored in 53 consecutive patients (control group). Then, quality improvement measures were implemented recommending a purging procedure before and after bolus administration of pantoprazole as a drug frequently causing incompatibilities in this setting. Additionally, the use of 4-lumen instead of 3-lumen catheters was suggested whenever considered useful by the responsible physicians. The monitoring was repeated during a second period in another 58 patients consecutively admitted to the same unit (intervention group). MAIN OUTCOME MEASURE: Overall number of patients with at least one incompatible drug pair and number of patients receiving incompatible pantoprazole combinations. RESULTS: The number of patients receiving incompatible pantoprazole combinations decreased from 15 of the 15 patients receiving pantoprazole (100.0%) in controls to 9/16 (56.2%) in the intervention group (P < 0.01). The overall number of patients with incompatibilities was not influenced by the intervention with 36/58 (62.1%) compared to controls with 38/53 (71.7%, P = 0.28). The fraction of central lines contributed by four lumen central catheters was larger due to the intervention (80/168 lines, 47.6%) compared to controls (16/184, 8.7%, P < 0.001). Only sporadically there were incompatible combinations of drugs governed by the already existing SOPs. CONCLUSION: In an intensive care setting with good SOP adherence, purging before and after administration decreased the respective incompatibility rate whereas the use of 4-lumen instead of 3- lumen catheters had not the expected benefit on separating drug pairs.

The XbaI G>T polymorphism of the glucose transporter 1 gene modulates 18F-FDG uptake and tumor aggressiveness in breast cancer.

UNLABELLED: We investigated the relevance of single-nucleotide polymorphisms (SNPs) in the glucose transporter 1 (GLUT1) gene to the uptake of (18)F-FDG and tumor aggressiveness in breast cancer. METHODS: In 52 individuals with breast cancer, a diagnostic PET/CT scan was obtained, and the standardized uptake value was determined as a measure of (18)F-FDG uptake using a region-of-interest technique. Three GLUT1 SNPs (XbaI G>T, HpyCH4V A>T, and HaeIII T>C) were investigated in genomic DNA that was isolated from the paraffin-embedded specimens of all patients. Tumors were typed and graded according to the World Health Organization classifications. RESULTS: The GG genotype of the XbaI G>T SNP was associated with increased tumor uptake of (18)F-FDG, with a mean standardized uptake value of 11.7 (TT/GT genotypes, 5.9; P = 0.03). Furthermore, the GG genotype was positively related to enhanced tumor proliferation (mitotic count, P = 0.01). In line with this finding, the GG genotype was absent in grade 1 carcinomas and increasingly prevalent in tumors with higher malignancy (grade 2, 28.0%; grade 3, 50%; P = 0.04). CONCLUSION: This study found that the XbaI G>T SNP of the GLUT1 gene is associated with an increased (18)F-FDG uptake and a more advanced tumor grade or growth in breast cancer. Thus, this genetic variant might favor aggressive phenotypes by modulating the efficiency of cancer cells to recruit glucose and escalate growth rate, suggesting the XbaI G>T SNP as a proliferation-related prognostic factor.

The influence of saliva flow stimulation on the absorbed radiation dose to the salivary glands during radioiodine therapy of thyroid cancer using 124I PET(/CT) imaging.

PURPOSE: A serious side effect of high-activity radioiodine therapy in the treatment of differentiated thyroid cancer is radiogenic salivary gland damage. This damage may be diminished by lemon-juice-induced saliva flow immediately after 131I administration. The aim of this study was to assess the effect of chewing lemon slices on the absorbed (radiation) doses to the salivary glands. METHODS: Ten patients received (pretherapy) 124I PET(/CT) dosimetry before their first radioiodine therapy. The patients underwent a series of six PET scans at 0.5, 1, 2, 4, 48 and ≥96 h and one PET/CT scan at 24 h after administration of 27 MBq 124I. Blood samples were also collected at about 2, 4, 24, 48, and 96 h. Contrary to the standard radioiodine therapy protocol, the patients were not stimulated with lemon juice. Specifically, the patients chewed no lemon slices during the pretherapy procedure and neither ate food nor drank fluids until after completion of the last PET scan on the first day. Organ absorbed doses per administered 131I activity (ODpAs) as well as gland and blood uptake curves were determined and compared with published data from a control patient group, i.e. stimulated per the standard radioiodine therapy protocol. The calculations for both groups used the same methodology. RESULTS: A within-group comparison showed that the mean ODpA for the submandibular glands was not significantly different from that for the parotid glands. An intergroup comparison showed that the mean ODpA in the nonstimulation group averaged over both gland types was reduced by 28% compared to the mean ODpA in the stimulation group (p=0.01). Within each gland type, the mean ODpA reductions in the nonstimulation group were statistically significant for the parotid glands (p=0.03) but not for the submandibular glands (p=0.23). The observed ODpAs were higher in the stimulation group because of increased initial gland uptake rather than group differences in blood kinetics. CONCLUSION: The 124I PET(/CT) salivary gland dosimetry indicated that lemon juice stimulation shortly after 131I administration in radioiodine therapy increases the absorbed doses to the salivary glands.

Diagnostic value of diffusion-weighted magnetic resonance imaging (DWI) compared to FDG PET/CT for whole-body breast cancer staging.

PURPOSE: The aim of the study was to prospectively compare the diagnostic value of whole-body diffusion-weighted imaging (DWI) and FDG PET/CT for breast cancer (BC) staging. METHODS: Twenty BC patients underwent whole-body FDG PET/CT and 1.5-T DWI. Lesions with qualitatively elevated signal intensity on DW images (b = 800 s/mm(2)) were rated as suspicious for tumour and mapped to individual lesions and different compartments (overall 552 lesions). The apparent diffusion coefficient (ADC) value was determined for quantitative evaluation. Histopathology, MRI findings, bone scan findings, concordant findings between FDG PET/CT and DWI, CT follow-up scans and plausibility served as the standards of reference defining malignancy. RESULTS: According to the standards of reference, breasts harboured malignancy in 11, regional lymph nodes in 4, M1 lymph nodes in 3, bone in 7, lung in 2, liver in 3 and other tissues in 3 patients. On a compartment basis, the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for the detection of malignancies were 94, 99, 98, 97 and 98% for FDG PET/CT and 91, 72, 76, 50 and 96% for DWI, respectively. Of the lesions seen on DWI only, 348 (82%) turned out to be false-positive compared to 23 (11%) on FDG PET/CT. The average lesion ADC was 820 +/- 300 with true-positive lesions having 929 +/- 252 vs 713 +/- 305 in false-positive lesions (p < 0.0001). CONCLUSION: Based on these initial data DWI seems to be a sensitive but unspecific modality for the detection of locoregional or metastatic BC disease. There was no possibility to quantitatively distinguish lesions using ADC. DWI alone may not be recommended as a whole-body staging alternative to FDG PET(/CT). Further studies are necessary addressing the question of whether full-body MRI including DWI may become an alternative to FDG PET/CT for whole-body breast cancer staging.