Since its introduction in the early nineties as a promising functional imaging technique in the management of neoplastic disorders, FDG-PET, and subsequently FDG-PET/CT, has become a cornerstone in several oncologic procedures such as tumor staging and restaging, treatment efficacy assessment during or after treatment end and radiotherapy planning. Moreover, the continuous technological progress of image generation and the introduction of sophisticated software to use PET scan as a biomarker paved the way to calculate new prognostic markers such as the metabolic tumor volume (MTV) and the total amount of tumor glycolysis (TLG). FDG-PET/CT proved more sensitive than contrast-enhanced CT scan in staging of several type of lymphoma or in detecting widespread tumor dissemination in several solid cancers, such as breast, lung, colon, ovary and head and neck carcinoma. As a consequence the stage of patients was upgraded, with a change of treatment in 10%–15% of them. One of the most evident advantages of FDG-PET was its ability to detect, very early during treatment, significant changes in glucose metabolism or even complete shutoff of the neoplastic cell metabolism as a surrogate of tumor chemosensitivity assessment. This could enable clinicians to detect much earlier the effectiveness of a given antineoplastic treatment, as compared to the traditional radiological detection of tumor shrinkage, which usually takes time and occurs much later.
PET/CT-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analyzed the clinicopathologic correlations and prognostic meaning of different patterns of bone marrow (BM) 18 F-FDG uptake in HL. Methods: One hundred eighty newly diagnosed early unfavorable and advanced-stage HL patients, all scanned at baseline and after 2 adriamycin-bleomycinvinblastine-dacarbazine (ABVD) courses with 18 F-FDG PET, enrolled in 2 international studies aimed at assessing the role of interim PET scanning in HL, were retrospectively included. Patients were treated with ABVD · 4-6 cycles and involved-field radiation when needed, and no treatment adaptation on interim PET scanning was allowed. Two masked reviewers independently reported the scans. Results: Thirty-eight patients (21.1%) had focal lesions (fPET 1 ), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three patients (29.4%) had pure strong (.liver) diffuse uptake (dPET 1 ) and 89 (48.4%) showed no or faint (#liver) BM uptake (nPET 1 ). BM biopsy was positive in 6 of 38 patients (15.7%) for fPET 1 , in 1 of 53 (1.9%) for dPET 1 , and in 5 of 89 (5.6%) for nPET 1 . dPET 1 was correlated with younger age, higher frequency of bulky disease, lower hemoglobin levels, higher leukocyte counts, and similar diffuse uptake in the spleen. Patients with pure dPET 1 had a 3-y progression-free survival identical to patients without any 18 F-FDG uptake (82.9% and 82.2%, respectively, P 5 0.918). However, patients with fPET1 (either unifocal or multifocal) had a 3-y progressionfree survival significantly inferior to patients with dPET1 and nPET1 (66.7% and 82.5%, respectively, P 5 0.03). The k values for interobserver agreement were 0.84 for focal uptake and 0.78 for diffuse uptake. Conclusion: We confirmed that 18 F-FDG PET scanning is a reliable tool for BMI assessment in HL, and BM biopsy is no longer needed for routine staging. Moreover, the interobserver agreement for BMI in this study proved excellent and only focal 18 F-FDG BM uptake should be considered as a harbinger of HL.
Perturbation of thyroid iodide uptake is a well-documented side effect of the use of iodinated contrast media (ICM) administered intravenously. This side effect is thought to be mediated by free iodide in ICM formulations, but this hypothesis has never been formally proven. The aim of the present study was to assess the validity of this hypothesis. We used mass spectrometry analysis to quantify free-iodide contamination in ICM. Established cell lines expressing the Na/I symporter (NIS) were used to quantify the effect of ICM on iodide uptake. SPECT/CT was used to measure the in vivo uptake ofTc-pertechnetate and I in 2 NIS-expressing mouse tissues, thyroid and salivary glands. Scintiscans of ICM-naïve and ICM-administered patients were compared. Immunohistologic and Western blot analyses were performed to evaluate NIS protein expression in these organs. Although free iodide was present in ICM formulations, in vitro uptake of iodide by NIS-expressing cells was not significantly affected by ICM. In mice, intravenous or sublingual administration of ICM led to a reduction in radiotracer uptake by the thyroid, accompanied by a dramatic reduction in NIS protein expression in this tissue. In the salivary glands, neither radiotracer uptake nor NIS protein expression was affected by ICM. The thyroid-selective effect of ICM was also observed in humans. Administration of potassium iodide as a source of free iodide led to a diminution of Tc-pertechnetate uptake in both mouse thyroid and mouse salivary glands. Altogether, these data rule out a direct intervention of free iodide in the perturbation of thyroid uptake and suggest a direct and selective effect of ICM on the thyroid. We demonstrated that ICM reduce thyroid uptake of iodide independently of free iodide. This effect is due to a specific and dramatic decrease in NIS expression in thyrocytes. These data cast serious doubt on the relevance of measuring urinary iodide concentration to evaluate the delay between ICM administration and radioiodine therapy in patients with differentiated thyroid carcinoma. Finally, the ability of ICM to perturb iodide uptake in the thyroid may be used in radioprotection.
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