The aim of this study was to evaluate the use of [(18)F]fluorothymidine (FLT) as a positron emission tomography (PET) tracer for the diagnosis of breast cancer. To this end, 12 patients with 14 primary breast cancer lesions (T2-T4) were studied by FLT-PET. For comparison, [(18)F]fluorodeoxyglucose (FDG) PET scans were performed in six patients. Thirteen of the 14 primary tumours demonstrated focally increased FLT uptake (SUV(mean)=3.4+/-1.1). Seven out of eight patients with histologically proven axillary lymph node metastases showed focally increased FLT uptake in the corresponding areas (SUV(mean)=2.4+/-1.2). The lowest SUV (mean =0.7) was observed in one of two inflammatory cancers. The contrast between primary tumours or metastases and surrounding tissue was high in most cases. In direct comparison to FDG-PET, the SUVs of primary tumours (5/6) and axillary lymph node metastases (3/4) were lower in FLT-PET (SUV(FLT): 3.2 vs SUV(FDG): 4.7 in primary tumours and SUV(FLT): 2.9 vs SUV(FDG): 4.6 in lymph node metastases). Since FLT uptake in surrounding breast tissue was also lower, tumour contrast was comparable to that with FDG. It is of note that normal FLT uptake was very low in the mediastinum, resulting in a higher tumour-to-mediastinum ratio as compared to FDG ( P=0.03). FLT-PET is suitable for the diagnosis of primary breast cancer and locoregional metastases. High image contrast may facilitate the detection of small foci, especially in the mediastinum.

This study evaluated the use of 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) for monitoring of the early effects of anticancer chemotherapy on tumour cell proliferation. Cells derived from human oesophageal squamous cell carcinoma (OSC-1) were grown for 2 days and incubated with cisplatin (CDDP), 5-fluorouracil (5-FU), methotrexate (MTX) or gemcitabine (GEM) for 4 h. Cultures were incubated with drug doses (CDDP: 0.67, 6.7, 67 micro M; 5-FU 15.4, 154, 1,540 micro M; MTX: 4.4, 44, 440 micro M; GEM: 0.0067, 0.067, 0.67 micro M) corresponding to approximately 10%-95% proliferation inhibition (MTX: 10%-75%). Treatment was stopped and cells were allowed to recover for 4, 24 or 72 h. [(18)F]FLT was added for 10-180 min. Control cultures were incubated with [(18)F]fluorodeoxyglucose (FDG). Cell counts, viability, clonogenic activity and cell cycle distribution estimated by flow cytometry were used to evaluate the cytotoxic effects of chemotherapy. Strikingly, FLT uptake per 10(5) viable cells was increased seven- to tenfold 24 h after treatment with 5-FU or MTX irrespective of dose. Thus, total FLT uptake per tissue culture exceeded that of controls despite a considerable decrease in overall cell counts due to cytostasis up to 72 h after treatment. 5-FU-treated cells showed accumulation in early S phase (overall S phase: 88% vs 42%). GEM treatment resulted in a more moderate increase in total FLT accumulation, to a maximum of fivefold at the dose close to the IC(50). In contrast, FLT accumulation was significantly reduced at cytostatic concentrations of CDDP and was still decreasing in a dose-related manner at 72 h despite considerable S phase arrest. With 5-FU or CDDP, the uptake of FDG did not differ significantly from control values 24 h after treatment. These findings demonstrate that tumour cell uptake of FLT - in contrast to that of FDG - reveals specific changes depending on the cytostatic drug used for treatment. The antimetabolites 5-FU and MTX massively increase FLT accumulation per cell independent of dose, i.e. cytotoxicity. Early after treatment, this increase is not predictive of proliferation inhibition but reflects activated salvage pathway of DNA synthesis. By contrast, CDDP results in an early decline in FLT but not in FDG uptake. This drug-specific modulation of FLT uptake has to be taken into account in positron emission tomography studies using FLT for treatment monitoring.

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The lung shunt fraction (LSF) is estimated using Tc-macroaggregated albumin (Tc-MAA) imaging before selective internal radiotherapy (SIRT) of the liver to reduce the risk of pulmonary irradiation. Generally, planar scans are acquired after injection of Tc-MAA into the hepatic artery. However, the validity of this approach is limited by differences in attenuation between liver and lung tissue as well as inaccurate segmentation of the organs. The aim of this study was to evaluate quantitative SPECT/CT for LSF assessment in a prospective clinical cohort. Fifty consecutive patients intended to undergo SIRT were imaged within 1 h after injection of Tc-MAA using a SPECT/CT γ-camera. Planar scans of the lung and liver region were acquired in anterior and posterior views, followed by SPECT/CT scans of the thorax and abdomen. Emission data were corrected for scatter, attenuation, and resolution recovery using dedicated software. To quantify the radioactivity concentration in the lung, liver, urinary bladder and remainder of the thoracoabdominal body, volumes of interest were defined on the SPECT/CT images.Tc-MAA concentrations were calculated as percentage injected dose (%ID). MeanTc-MAA uptake in liver and lung accounted for only 79 %ID, whereas 13.1 %ID was present in the remainder of the body. In all patients, LSF as calculated from planar scans accounted for a median of 6.8% (range, 3.4%-32.3%), whereas the SPECT/CT quantitation revealed significantly lower LSF estimates, at a median of 1.9% (range, 0.8%-15.7%) ( < 0.0001, Wilcoxon test). On the basis of planar imaging, dose reduction or even contraindications to SIRT had to be considered in 10 of 50 patients, as their LSF was calculated at 10% or more. In contrast, SPECT/CT quantitation showed substantial shunting in only 2 of the 50 patients. Quantitative SPECT/CT reveals that the LSF is considerably lower than shown on planar imaging. Thus, the resulting dose to the lung parenchyma may be less than conventionally assumed. However, the safety of the SPECT/CT-derived dose range will have to be evaluated.

The nucleoside analogue 3'-deoxy-3'-[18F]fluorothymidine (FLT) has been introduced for imaging of tumour cell proliferation by positron emission tomography (PET). This study evaluated the use of FLT in patients with thoracic tumours prior to treatment. Whole-body FLT PET was performed in 16 patients with 18 tumours [17 thoracic tumours (nine non-small cell lung cancers, five oesophageal carcinomas, two sarcomas, one Hodgkin's lymphoma) and one renal carcinoma] before treatment. Fluorine-18 fluorodeoxyglucose (FDG) PET was performed for comparison except in those patients with oesophageal carcinoma. For semi-quantitative analysis, the average and maximum standardised uptake values (avgSUV and maxSUV, respectively) (FLT, 114+/-20 min p.i.; FDG, 87+/-8 min p.i.; 50% isocontour region of interest) was calculated. All 17 thoracic tumours and 19/20 metastases revealed significant FLT accumulation, resulting in easy delineation from surrounding tissue. The additional small grade 1 renal carcinoma was not detected with either FLT or FDG. In most lung tumours (avgSUV 1.5-8.2) and metastases, FLT showed intense uptake. However, one of two spinal bone metastases was missed owing to the high physiological FLT uptake in the surrounding bone marrow. Oesophageal carcinoma primaries (avgSUV 2.7-10.0) and occasional metastases showed particularly favourable tumour/non-tumour contrast. Compared with FDG, tumour uptake of FLT was lower (avgSUV, P=0.0006; maxSUV, P=0.0001), with a significant linear correlation (avgSUV, r2=0.45; maxSUV, r2=0.49) between FLT and FDG. It is concluded that FLT PET accurately visualises thoracic tumour lesions. In the liver and the bone marrow, high physiological FLT uptake hampers detection of metastases. On the other hand, FLT may be favourable for imaging of brain metastases owing to the low physiological uptake.

Sporadic primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient population, with a prevalence of one per 500 women and one per 2000 men over 40 years of age. Both increased cell proliferative activity and a decreased sensitivity of cells to secretory inhibition by calcium occur in hyperparathyroidism (1). The diagnosis of hyperparathyroidism is usually made by the demonstration of an inappropriately elevated parathyroid hormone level compared to the simultaneously measured serum calcium level (2). In 80% to 85% of patients, primary hyperparathyroidism is caused by one or more parathyroid adenomas, and in 15% to 20% of cases, it is the result of parathyroid hyperplasia. A rare cause of primary hyperparathyroidism, accounting for less than 1% of all cases, is parathyroid carcinoma. Persistent hyperparathyroidism occurs in 5% to 10% of all patients who undergo surgery for primary hyperparathyroidism, with a continuation of the pre-operative hypercalcemia in the immediate post-operative period. Hyperparathyroidism that presents after a period of more than six months of normocalcemia following surgery is called "recurrent hyperparathyroidism" and is commonly due to continuing growth of the remaining parathyroid glands (3). Secondary hyperparathyroidism is a compensatory hypertrophy of all parathyroid glands due to hypocalcemia, as occurs in renal failure or with vitamin D deficiency (4), whereas tertiary hyperparathyroidism describes the development of autonomous function of parathyroid tissue after longstanding secondary hyperparathyroidism (5-8).In most cases (80%-85%), parathyroid adenomas are found adjacent to the thyroid gland, which is the normal location for these adenomas. However, in up to 20% of cases, they are ectopically placed, e.g., in the anterosuperior, posterosuperior, or very rarely in the mid-lower mediastinum. Occasionally, parathyroid adenomas may be found within, or lateral to, the carotid sheath. Rarely, the lower parathyroid glands fail to migrate, remaining in the high neck anterior to the carotid bifurcation. Finally, 1.4% to 3.2% of all parathyroid adenomas are intrathyroidal, i.e., embedded completely within the thyroid gland (9).Among the several imaging procedures that have been developed for the detection and localization of parathyroid adenomas, dual-phase scintigraphy with Tc-99m sestamibi combined with ultrasonography is considered the imaging method of choice for pre-operatively localizing parathyroid adenomas. The overall accuracy of dual-phase scintigraphy combined with ultrasonography has been found to be superior to that of other scintigraphic or radiological techniques (10, 11). Studies comparing planar imaging and single photon emission computed tomography (SPECT) have shown significantly increased sensitivity for Tc-99m sestamibi SPECT, thus supporting its routine use prior to surgery (12-14). HEAD AND NECK IMAGING PURPOSETo compare the accuracy of planar scintigraphy, single photon emission computed tomography (SPECT), SPECT-CT, and positron...

Background: Attenuation correction (AC) of PET data is usually performed using a second imaging for the generation of attenuation maps. In certain situations however-when CT-or MR-derived attenuation maps are corrupted or CT acquisition solely for the purpose of AC shall be avoided-it would be of value to have the possibility of obtaining attenuation maps only based on PET information. The purpose of this study was to thus develop, implement, and evaluate a deep learning-based method for whole body [ 18 F]FDG-PET AC which is independent of other imaging modalities for acquiring the attenuation map. Methods: The proposed method is investigated on whole body [ 18 F]FDG-PET data using a Generative Adversarial Networks (GAN) deep learning framework. It is trained to generate pseudo CT images (CT GAN) based on paired training data of non-attenuation corrected PET data (PET NAC) and corresponding CT data. Generated pseudo CTs are then used for subsequent PET AC. One hundred data sets of whole body PET NAC and corresponding CT were used for training. Twenty-five PET/CT examinations were used as test data sets (not included in training). On these test data sets, AC of PET was performed using the acquired CT as well as CT GAN resulting in the corresponding PET data sets PET AC and PET GAN. CT GAN and PET GAN were evaluated qualitatively by visual inspection and by visual analysis of color-coded difference maps. Quantitative analysis was performed by comparison of organ and lesion SUVs between PET AC and PET GAN. Results: Qualitative analysis revealed no major SUV deviations on PET GAN for most anatomic regions; visually detectable deviations were mainly observed along the diaphragm and the lung border. Quantitative analysis revealed mean percent deviations of SUVs on PET GAN of − 0.8 ± 8.6% over all organs (range [− 30.7%, + 27.1%]). Mean lesion SUVs showed a mean deviation of 0.9 ± 9.2% (range [− 19.6%, + 29.2%]). Conclusion: Independent AC of whole body [ 18 F]FDG-PET is feasible using the proposed deep learning approach yielding satisfactory PET quantification accuracy. Further clinical validation is necessary prior to implementation in clinical routine applications.

Pre-therapeutic (68)Ga-DOTATOC tumor uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with the results of subsequent PRRT. The defined cut-off values should be confirmed by prospective studies and may then provide the rationale for individual dosing and selecting patients with high likelihood of favorable treatment outcome.