Residual Uptake Research Articles

Identification of residual metabolic-active areas within NSCLC tumours using a pre-radiotherapy FDG-PET-CT scan: A prospective validation

It was recently described that high FDG-uptake areas pre-radiotherapy largely correspond with residual metabolic-active areas post-radiotherapy. Here, an independent prospective validation of these results was performed using an overlap-fraction (OF) calculation of various FDG-uptake based thresholds. Data from twelve patients treated at Radboud University Nijmegen Medical Center with lung cancer were analyzed. All patients underwent two FDG-PET-CT scans, one pre-radiotherapy (pre-RT) and one approximately three months after treatment (post-RT). Of the twelve analyzed patients, eight patients showed residual FDG uptake on the post-RT scan and were included for analysis. One of these patients had a residue that was not clearly distinguishable from the surrounding tissue due to FDG avid inflammation. Therefore, seven patients remained for further analysis. The mean volume of the residual metabolic-active areas post-RT was 14.6±10.0% (mean±SD) of the mean volume of the gross tumour volume (GTV) pre-RT. The residual metabolic-active areas largely corresponded with the pre-RT GTV (OF=93.7±7.2%). The pre-RT-scan threshold delineations of 34%, 40% and 50% of the SUVmax had a large OF with the residual region, 86.9±8.3%, 77.4±8.1% and 67.9±6.8%, respectively. In this independent dataset, we confirmed that the location of residual FDG-uptake areas after radiotherapy corresponds with the high FDG-uptake areas pre-radiotherapy. Therefore, a pre-radiotherapy FDG-PET-CT scan can potentially be used for radiotherapy dose redistribution.

Phytotoxicity and uptake of chlorpyrifos in cabbage

Chinese cabbage, Brassica chinensis L., and cabbage, Brassica oleracea L. var. capitata, are the main daily foliar vegetables of the vast majority of the population of eastern and southern China. Cabbages are also planted and consumed widely in other countries. The insecticide and acaricide chlorpyrifos is registered in many countries. Chlorpyrifos controls a variety of insects in plants and soils, and chlorpyrifos is extensively used in the Chinese market. Food poisoning due to the presence of organophosphorus pesticide residues in vegetables has been reported in China provinces. Plant uptake of pesticide residues in air, water, and soil is a source of pesticide residues in vegetables. Here, phytotoxicity and uptake of chlorpyrifos by Chinese cabbage and cabbage were studied in the laboratory using the batch technique. From 0 to 16 days after chlorpyrifos treatment, vegetables roots, stems, leaves, and culture water samples were collected, and the residues of chlorpyrifos in culture water, plant tissues were analyzed using GC-FPD. The results demonstrate that culture solutions with chlorpyrifos had no significant inhibitory effects on vegetable plant height. However, at 1.0 mg/l, it had significant inhibitory effects on the root length and fresh weight of Chinese cabbage. Then, at 10.0 mg/l, it had only significant inhibitory effects on the root length and fresh weight of cabbage compared to the control treatment. The disappearance rates of chlorpyrifos in solutions were in sequence as: nutrition solution with Chinese cabbage, nutrition solution with cabbage, pond water, nutrition solution. The results showed also that chlorpyrifos can be taken up by roots of Chinese cabbage and cabbage from water and subsequently translocated as a function of time. Uptake dynamics of chlorpyrifos from culture solutions by the two cabbage plants were similar.

Total Thyroidectomy in the Mouse: the Feasibility Study in the Non-thyroidal Tumor Model Expressing Human Sodium/Iodide Symporter Gene.

This study sought to probe the feasibility of performing total thyroidectomy in the mouse using a non-thyroidal hNIS expressing tumor model. Our thyroidectomy protocol included thorough excision of both lobes and the isthmus. For evaluating the completeness of thyroidectomy, we compared the (99m)Tc-pertechnetate scans taken before and after thyroidectomy. The prostate cancer cell line was subcutaneously inoculated 2weeks after the thyroidectomy. When the tumor reached 5-10mm in diameter, Ad5/35-E4PSESE1a-hNIS was injected intratumorally, and (131)I scans were performed. The radioiodine uptakes of the neck and the tumor were compared with those of the other regions. Total thyroidectomy was performed in 13 mice. Although 38.5% died during or just after thyroidectomy, the others survived in good health for 2months. Thyroid tissue was completely eliminated using our protocol; the residual uptake of (99m)Tc-pertechnetate was minimal in the neck area. The neck/background uptake ratio after thyroidectomy was significantly lower than that before thyroidectomy (p < 0.05). Non-thyroidal tumor models were successfully established in all the surviving mice. Radioiodine accumulation in the tumors was visualized on (131)I scans, and the neck uptakes were minimal. Using our total thyroidectomy protocol, we successfully established a hNIS-transfected prostate cancer model with a minimal accumulation of radioiodine in the neck. The relatively high mortality after surgery can be a problem, and this might be reduced by minimizing the surgical stress.

Prognostic value of interim FDG PET/CT in Hodgkin’s lymphoma patients treated with interim response-adapted strategy: comparison of International Harmonization Project (IHP), Gallamini and London criteria

Interim 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) has shown to be an accurate predictor of prognosis in Hodgkin's lymphoma (HL). However, FDG PET response criteria are a matter of ongoing debate. The aim of this study was to confirm the prognostic value of interim PET/CT in HL patients treated with an interim response-adapted strategy and to compare the respective performances of different published criteria. Newly diagnosed patients with HL underwent interim PET/CT after four courses of Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). The treatment strategy was adapted according to prognostic factors at diagnosis and interim PET/CT and CT results. PET images were prospectively interpreted visually: a negative result was defined as no residual uptake above local background. All other findings were considered as positive. Retrospectively, interim PET/CT was analysed according to International Harmonization Project (IHP), Gallamini and London criteria The analysis included 90 patients; 6 of 31 patients with positive interim PET/CT and 7 of 59 patients with negative interim result presented treatment failure. The negative predictive value (NPV) and positive predictive value (PPV) for predicting 2-year progression-free survival (PFS) was 95 and 16%, respectively. With the other criteria, NPV remained very high (from 95 to 96%). The PPV increased from 19 to 45% according to the threshold used. Interim PET/CT was significantly correlated with PFS with Gallamini (p = 0.01) and London criteria (p < 0.0001). Our study confirms the high NPV of interim PET/CT for predicting treatment outcome in HL and a probably better prognostic value using a higher threshold for positivity even after four cycles of chemotherapy as used in Gallamini and London criteria.

Undetectable Thyroglobulin in Patients With Differentiated Thyroid Carcinoma and Residual Radioiodine Uptake on a Postablation Whole-Body Scan

To assess the impact of laboratory interferences and pitfalls in producing falsely undetectable Tg in differentiated thyroid carcinoma (DTC) patients with residual iodine-avid thyroid tissue on a posttreatment whole-body scan (PT-WBS). From 298 consecutive patients with histologically proven DTC, 47 patients (16%) with undetectable serum Tg but residual ¹³¹I uptake on a PT-WBS were selected. Interferences from antithyroglobulin antibodies (TgAb), heterophile antibodies, and hook-effects were screened; in the remaining samples, serum Tg was measured in 3 different immunoassays. Of 47 patients, 11 (23%) showed interference from either thyroglobulin antibodies (n = 10) or heterophile antibodies (n = 1). Among the 36 remaining patients, 18 showed detectable Tg levels after retesting using a different immunoassay, whereas the remaining 18 patients also showed detectable Tg levels in a third Tg immunoassay. However, only 7 patients showed a detectable Tg in both secondarily used assays. Tg levels remained undetectable in all methods in 9 patients (19%) even after extensive laboratory work-up and despite the presence of ¹³¹I-avid tissue found in PT-WBS. A careful assessment of interferences in Tg measurement significantly reduced the occurrence of undetectable Tg among patients with ¹³¹I uptake in PT-WBS. However, such extensive assessment is difficult in clinical practice and one-fifth of patients still had undetectable Tg in multiple assays despite an intensive laboratory work-up. A benchmark between ¹³¹I imaging and Tg measurement authenticates the interpretation of Tg measurements and, consequently, remains of pivotal value by authenticating the use of serum Tg during further follow-up of DTC patients.

Storage of carbon dioxide captured in a pilot-scale biogas upgrading plant by accelerated carbonation of industrial residues

This work reports the preliminary evaluations obtained within the UPGAS-LOW CO2 project (LIFE08 ENV/IT/000429) concerning innovative methods for biogas upgrading through CO2 capture and storage. One of the methods studied in this project is chemical absorption of the CO2 contained in landfill gas with a KOH solution followed by carbonation of the spent solution with selected industrial residues to regenerate the alkaline solution and store CO2 in a solid phase (calcite). This paper presents the main results of the lab scale experiments carried out to evaluate the effects o f the main operating parameters on the carbonation reaction so to identify the conditions that allow to maximize the CO2 uptake of the solid residues and the percentage of KOH that can be regenerated for the absorption process. These results provide the dataset for the design of a pilot plant unit to be built and operated in the follow-up of the project.

Interim FDG-PET Scan in Hodgkin's Lymphoma: Hopes and Caveats

FDG-PET has recently emerged as an important tool for the management of Hodgkins lymphoma. Although its use for initial staging and response evaluation at the end of treatment is well established, the place of interim PET for response assessment and subsequent treatment tailoring is still quite controversial. The use of interim PET after a few cycles of chemotherapy may allow treatment reduction for good responders, leading to lesser treatment toxicities as well as early treatment adaptation for bad responders with a potential higher chance for cure. Interpretation of interim PET is a rapidly moving field. Actually, visual interpretation is preferred over quantitative interpretation in this situation. The notion of minimal residual uptake emerged for faint persisting FDG uptake, but has evolved during the recent years. Guidelines using mediastinum and liver as references have been proposed at the expert meeting in Deauville 2009. Actually, several trials are ongoing both for localised and advanced disease to evaluate the FDG-PET potential for early treatment monitoring and tailoring. Until the results of these prospective randomized trials become available, treatment changes according to the interim PET results should remain inappropriate and limited to well-conducted clinical trials.

Abstract P5-01-06: 18[F]-FDG Tumoral Uptake and Metabolic Response after 1 Cycle of Primary Chemotherapy According to Tumoral Phenotype of Breast Cancer

Abstract To compare the 18[F]-FDG-PET (PET) metabolic characteristics in triple-negative, luminal and positive HER2 breast cancer. Material and Methods: One hundred and forty-five patients with newly diagnosed locally advanced breast cancer were evaluated. Twenty one metastatic patients (discovered in baseline PET) were excluded and 9 patients were lost. One hundred and fifteen had undergone FDG PET before and after the first course of neoadjuvant chemotherapy. Breast cancer lesions were imaged at 80-90 minutes after administration of FDG. Maximum standardized uptake values (SUV) were measured at both time point (SUV1 and SUV 2). Metabolic response was measured by the relative decrease of SUV (ΔSUV). Using Immunohistochemistry as a surrogate for expression profiling, the tumours were classified as follows: triple negative defined by the lack of oestrogen receptors, progesterone receptors and human epidermal growth factor receptors 2 (HER2) expression, luminal (hormonal receptor positive, HER2 negative) and HER2 positive (overexpression of HER 2). Relationships between baseline [18F]-FDG uptake and clinical, histopathological and biological parameters were assessed by Mann-Whitney test. Relationships between SUV1, SUV2, ΔSUV and the tumoral phenotype were assessed by Kruskal-Wallis test. Results: In the overall population the mean ±SD SUV1, SUV2 and ΔSUV values were 6.7± 5.9, 3.7± 3 and −36.7% ± 35.7%, respectively. Significant relationships were found between baseline FDG uptake and initial clinical and histopathological parameters : a high mitotic activity (p≥0.0001), a high nuclear pleomorphism (≥0.0002), a high tumour grading (p≥0.0001) and a negative oestrogen hormonal receptor status (p≥0.0001) were associated with a high baseline SUV. Patient age, lymph node involvement, architectural differentiation, progesterone hormonal receptor and HER2 status were not found to be related with SUV values. Metabolic characteristics (mean ± SD) according to tumoral phenotype: Conclusion: Our results show a significant positive relationship between the baseline FDG uptake and the proliferation markers, the tumour grading, the number of mitoses and the nuclear pleomorphism. A significant negative relationship was found between the baseline FDG uptake and the oestrogen hormonal receptor status. The triple negative phenotype was associated with higher baseline FDG uptake and higher residual FDG uptake after one course of chemotherapy commensurate with their aggressive biology. Luminal tumours showed a lower ΔSUV reflecting their lower chemosensibility. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-06.

Impact of soil water regime on degradation and plant uptake behaviour of the herbicide isoproturon in different soil types

The environmental fate of the worldwide used herbicide isoproturon was studied in four different, undisturbed lysimeters in the temperate zone of Middle Europe. To exclude climatic effects due to location, soils were collected at different regions in southern Germany and analyzed at a lysimeter station under identical environmental conditions. 14C-isoproturon mineralization varied between 2.59% and 57.95% in the different soils. Barley plants grown on these lysimeters accumulated 14C-pesticide residues from soil in partially high amounts and emitted 14CO 2 in an extent between 2.01% and 13.65% of the applied 14C-pesticide. Plant uptake and 14CO 2 emissions from plants were inversely linked to the mineralization of the pesticide in the various soils: High isoproturon mineralization in soil resulted in low plant uptake whereas low isoproturon mineralization in soil resulted in high uptake of isoproturon residues in crop plants and high 14CO 2 emission from plant surfaces. The soil water regime was identified as an essential factor that regulates degradation and plant uptake of isoproturon whereby the intensity of the impact of this factor is strongly dependent on the soil type.

Interim-PET Scan Interpretation In the Ongoing Prospective Clinical Trial HD 0607, In Advanced-Stage Hodgkin Lymphoma: Results of the the Expert Panel Review

AbstractAbstract 3891 Background:several PET response-adapted prospective clinical trials are running at the moment, aimed at assessing the role of chemotherapy intensification in ABVD-treated Hodgkin Lymphoma (HL) patients with interim PET-positive after 2 cycles (PET-2). Standard interim-PET interpretation rules are still lacking, and expert review panels for PET interpretation have been implemented in these trials. We report here the results of PET-2 review in the HD 0607 trial. Patients and methods:starting from July 2008 till now, 236 advanced-stage HL patients have been consecutively enrolled in the Italian GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter clinical trial HD 0607 (NCT Identifier: NCT00795613). Advanced-stage (IIB-IVB) HL patients are first treated with 2 ABVD courses and PET-2 performed afterwards. All the non-negative PET-2 scan are reviewed by the expert panel. Non-negative PET-2 is defined as any scan with any residual FDG uptake outside the physiological areas of the tracer concentration. All the non-negative PET-2 according to the local centers (PET-2loc) are uploaded on the dedicated website (http://magic5.to.infn.it/gitil), along with the baseline scans. Six independent reviewers re-interpret the scans according to the 5-point semiquantitative score with mediastinum and liver as reference organs for residual fluorodeoxyglucose (FDG) uptake (Deauville score, Meignan 2009). The first three reviewers replying within 72 hours from PET upload determine the panel final decision; the remaining three report the scans later. Patients with a score 4 or 5 shifted to BEACOPP or Rituximab-BEACOPP escalated treatment; patients with score 1–3 continued with ABVD. Patient with bulky lesion (defined as a nodal mass with the largest diameter 3 6 cm) were treated with IF-RT. Results:199/236 patients performed a PET-2 scan: 131 (66%) showed a negative, 68 (33%) a non-negative scan. These 68 PET-2loc were reviewed (PET-2rev.); the clinical characteristics of patients with a reviewed and unreviewed PET-2loc were the following: mean age 32 vs.35, Stage III 19/68 (28%) and 61/131(46%), Stage IV 26/68 (39%) and 45/131 (34%), Bulky 44/68 (65%) and 93/131 (71%), IPS 3 or more 20/68 (29%) and 20/131 (15%), respectively. As a result of review there were 32 positive PET-2rev. and 36 negative PET-2rev. The median PET-2 review time from the uploading in the website to the third reviewer's report was 48 hours (1-90). The 32 positive PET-2rev scans showed a single residual focus in 28 and multiple foci of residual FDG uptake in 4 cases (all score 5). 22 showed a single lesion in the mediastinum, 4 in superficial lymph nodes and 2 in the lung. In 25/28 (89%) patients the single residual FDG uptake was within a bulky lesion and in 3/28 was outside it. The concordance rate among couples of reviewers for a positive vs. negative scan, measured with Cohen's Kappa, ranged between 0.76 (substantial agreement) and 0.92 (almost perfect agreement). The overall concordance rate measured with Krippendorf's Alpha, (assuming chance = 0 and perfect agreement =1) was 0.82. Lower concordance among reviewers was found in scans showing FDG residual uptake in anatomical structures not clearly related to lymphoma (brown fat, large vessels, bowel, tonsil, and inflammatory lung lesions). Conclusions:these data show that (1) the preliminary reports of a very high binary and overall concordance rate among reviewers using the Deauville score for PET-2 reporting (Barrington 2010) have been confirmed; (2) the online review process for PET-2 scan is feasible and simple; (3) most of the positive PET-2 scan showed a residual FDG uptake in the site of bulky disease, mostly in mediastinum. Disclosures:No relevant conflicts of interest to declare.

Respective PROGNOSTIC Value of the International Harmonization PROJECT (IHP), Gallamini and London Criteria for Interim FDG PET-CT Performed AFTER 4 Courses of ABVD IN HODGKIN'S LYMPHOMA

AbstractAbstract 3889During the last decade, the role of Interim 2-[18F]fluoro-2-deoxy-D-glucose emission positron tomography (FDG PET-CT) has increased for Hodgkin's lymphoma (HL) evaluation and it is strongly recommended for both staging and post treatment evaluation. Early treatment response assessment is a challenge for risk-adapted therapy and interim PET-CT has emerged as a powerful prognostic tool to predict treatment outcome, a negative exam predicting a favorable disease-free survival while a positive study a worse prognosis. However, FDG PET response criteria are a matter of ongoing debate. So, the aim of our study was to confirm the prognostic value of interim FDG PET-CT performed after 4 courses of chemotherapy (ABVD) but also to compare the respective performances of the different published criteria: International Harmonization Project (IHP), Gallamini criteria, 5-point scale (Gallamini A et al. Haematologica 2006; 91: 475–481; Juweid ME et al. J Clin Oncol 25:571-578, 2007; Barrington SF et al. Eur J Nucl Med Mol Imaging 2009;36(Suppl. 2):S252; Meignan M et al. Leukemia & Lymphoma, August 2009; 50(8): 1257–1260; Gallamini A, et al. Leuk Lymphoma. 2009 Nov;50(11):1761-4.) Design and methods:From 2002 to 2006, newly diagnosed patients with HL who underwent interim PET-CT after 4 courses of ABVD were eligible for the purpose of the present study. Treatment strategy after 4 courses of ABVD was then adapted according to prognostic factors at diagnosis and interim PET-CT result. PET images were interpreted prospectively visually by at least two nuclear medicine physicians with expertise in lymphoma imaging with the criteria used before 2005: negative result was defined as no residual uptake above local background. All other findings were considered as positive. Using these evaluation criteria, interim PET positive patients who were not in CR on CT underwent autologous stem cell transplantation. Interim PET positive patients who reached CR on CT and interim PET negative patients received additional courses of ABVD (patients with advanced HD or bulky disease at diagnosis) or radiotherapy alone (stage I or II without bulky disease). Retrospectively and for the purpose of the present study, interim PET results were interpreted using the more recent criteria (Gallamini criteria, IHP criteria and 5-point scale method) Results:90 patients were included. Median age at diagnosis was 34.4 (16-71). 49% of the patients presented with B-symptoms and 50% had stage III-IV disease. According to initial criteria, 31 patients had a positive interim PET result. Among these patients, 28 underwent ASCT. Fifty-nine patients had a negative interim PET-CT. Six of 31 patients with positive interim PET-CT and 7 of 59 patients with negative interim result presented treatment failure. Thus, the negative predictive value (NPV) and positive predictive value (PPV) for predicting 2 years progression free survival (PFS) was 95% and 16%, respectively. Retrospectively, interim PET-CT was analyzed according to different recent published criteria using mediastinum and liver background as threshold for positivity. With these criteria, NPV remained very high (from 95% to 96%). However, the PPV increased from 25% to 55% according to the threshold used. Taken together, the statistical analysis revealed that Interim PET-CT was significantly correlated with PFS only for two methods: the Gallamini criteria and the 5-point scale method. Conclusion:The first part of our study using the criteria used before 2005 shows the high NPV of interim PET-CT for predicting treatment outcome in HL. However, better prognostic values are obtained by using higher threshold for positivity such as liver background even after 4 cycles of ABVD. Indeed, our analysis underscores the better results reached by the Gallamini criteria and 5-point scale methods. The better method to predict PFS was obtained by the 5-point scale (scores 1, 2, 3 and 4 were classified as negative while only score 5 was classified as positive) showing a PPV and NPV of 55% and 96%, respectively. Disclosures:No relevant conflicts of interest to declare.

Tailored Therapy In Hodgkin Lymphoma, Based on Predefined Risk Factors and Early Interim PET/CT, Can Lead to Modification and Safe Reduction In Therapy: Results of 134 Patients on the Israel National Hodgkin Study.

AbstractAbstract 2809The current aim of treatment for Hodgkin lymphoma (HL) is to maximize response and minimize long term toxicity. This study prospectively evaluates the outcome of patients with HL whose therapy is chosen based on baseline prognostic factors and is tailored based on results of PET/CT imaging performed after 2 cycles of chemotherapy. In this multicenter study, initiated in 2006, we reduce the intensity of therapy for early responders and escalate the intensity for those with suboptimal early response. Patients with classic HL aged 18–60 years, I-IV are eligible. Those with early disease are categorized according to the German Hodgkin study group criteria for early favorable and unfavorable disease. Following 2 cycles of ABVD, patients with early favorable disease and a negative PET/CT undergo involved nodal radiation therapy (INRT) and those with early unfavorable disease receive 2 more cycles of ABVD (total of 4 cycles) followed by INRT. Patients whose interim PET/CT remains positive are given 2 additional cycles of ABVD for a total of 4 or 6 cycles followed by radiation therapy. Patients with advanced disease including all those with B symptoms or stages III and IV are assigned treatment according to the International Prognostic Score (IPS). Standard risk patients (IPS score 0–2) are initially treated with 2 cycles of ABVD and those with IPS score of ≥ 3 receive 2 cycles of escalated BEACOPP (EB). If interim PET/CT is negative or shows minimal residual uptake in no more than a single site then further therapy with 4 cycles of ABVD is administered and radiation therapy to bulky mediastinal mass is omitted. If interim PET/CT is positive but there no evidence of disease progression then therapy is escalated to EB with radiation therapy given to bulky mediastinal mass. 153 patients enrolled, of which 134 reached their interim imaging. Table 1 shows the number of patients in each risk group, positive predictive value of interim positive PET/CT and negative predictive value of negative study. Six patients had disease progression, two of them had primary refractory disease. One patient succumbed during autologous bone marrow transplantation. After a short follow up, median 20 month (6-50), the current study appears to demonstrate progression free survival (PFS) of 95%. The negative predictive value for the patient with negative interim study was 96% demonstrating that de-escalation is feasible and safe for patients with interim negative imaging. Further follow up and a larger cohort is needed to draw conclusions regarding the PFS of patients with interim positive PET/CT study as well as the long term toxicity.Table 1Risk group scorenPositive interim PET/CTNegative interim PET/CTProgressionTotalProgressionTotalNo ProgressionAll patients1521821181146 (4%)Early favorable1520660Early unfavorable702155533 (4%)Advanced disease67Score 0–2382031292 (5%)Score ≥3296120201 (3%) Disclosures:No relevant conflicts of interest to declare.

FDG Uptake Quantified with FDG PET 10-12 Days after Radiotherapy or Chemoradiotherapy in Lung Cancer is Molecular-Biomarker Capable for Predicting Therapy Outcome and Identifying Patients in Need for Timely Salvage Therapy

FDG uptake in living cells requires phosphorylation of FDG to FDG-6-phosphate. Thus, absence of FDG uptake may reflect cell's inability to continue cell's glucose metabolism. The goals of this study were: (1). To determine FDG uptake at sequential intervals after radiotherapy (RT) for primary lung cancer, (2). Determine the relationship between residual FDG uptake after RT and clinical outcome at 12 months (m), (3). Determine the levels of residual FDG uptake after RT that correlate with ≥ 95%, 90%, 75% and 50% tumor control probability (TCP) at 12 m.

Diagnostic and prognostic impact of 18F-FDG PET/CT in follicular lymphoma

The aim of this study was to assess the usefulness of positron emission tomography/computed tomography in staging, prognosis evaluation and restaging of patients with follicular lymphoma. A retrospective study was performed on 45 patients with untreated biopsy-proven follicular lymphoma who underwent 18F-fluorodeoxyglucose PET/CT (FDG PET/CT) and CT before and after chemoimmunotherapy induction treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone). PET/CT detected more nodal (+51%) and extranodal (+89%) lesions than CT. PET/CT modified Ann Arbor staging in eight patients (18%). Five patients (11%) initially considered as being early stage (I/II) were eventually treated as advanced stage (III/IV). In this study, an initial PET/CT prognostic score was significantly more accurate than the Follicular Lymphoma International Prognostic Index score in identifying patients with poor prognosis (i.e. patients with incomplete therapeutic response or early relapse). The accuracy of PET/CT for therapeutic response assessment was higher than that of CT (0.97 vs 0.64), especially due to its ability to identify inactive residual masses. In addition, post-treatment PET/CT was able to predict patients' outcomes. The median progression-free survival was 48 months in the PET/CT-negative group as compared with 17.2 months for the group with residual uptake (p<10(-4)). FDG PET/CT is useful for staging and assessing the prognosis and therapeutic response of patients with follicular lymphoma.

Interim PET in lymphoma: a step towards standardization

In this issue, Barrington et al. propose well-defined criteriafor interim PET/CT reporting in lymphoma [1]. Thesecriteria, based on a five-point scale, introduce two mainconcepts which are highly relevant for interim PETanalysis: (1) the intensity of the residual uptake frequentlyobserved at interim is graded relative to various levels ofreference background (RB)—mediastinal blood pool(MBP) and liver—and (2) this grading process is indepen-dent of the size of the residual tumour. Furthermore, theauthors reported that this five-point scale assessed on asample of 50 patients with advanced stage Hodgkin’slymphoma (HL) by 4 pairs of experts from 4 Europeancentres: (1) seems a reproducible tool for guiding thera-peutic strategy after 2 cycles of ABVD (Adriamycin,bleomycin, vinblastine, dacarbazine) when liver is chosenas an RB and (2) is robust enough to be used in multicentretrials for interim PET reporting.The authors have decided to use this scale in theResponse Adapted Treatment in Hodgkin Lymphoma(RATHL) trial, an interim PET-driven therapeutic strategyin patients with advanced stage HL. Although manytrials are ongoing worldwide in HL and non-Hodgkin’slymphoma (NHL) to test whether the results of an interimPET performed after one to four cycles of chemotherapycan tailor a response-adapted therapy, standardized interimPET criteria are still missing. Interim PET requires indeedspecific criteria which should be different from thosedefined for end treatment by the International Harmoniza-tion Project (IHP) in Lymphoma [2]. In the context of drugdevelopment and survival improvement observed inlymphoma, the rationale of interim PET is to define ana posteriori prognostic index reflecting tumour chemo-sensitivity during first-line therapy, allowing earlychanges of therapy (escalation or de-escalation) adaptedto specific situations. In many trials the strategy can bemodified according to the results of two interim PETexams performed at different times during inductiontreatment. As a matter of fact, depending on thecharacteristics of tumour growth and histological typethe evolution of PET under treatment is different. Indiffuse large B-cell lymphoma (DLBCL) neoplastic cellsconstitute more than 90% of the total cell population.The metabolic activity during therapy decreases in acontinuous mode, with cell killing. Interim PET after oneor two cycles of chemotherapy evaluates the response ofthe cells with the highest mitotic index, thereby providingan early evaluation of chemosensitivity and identifyingresponders and non-responders [3, 4]. On the other hand,after three or four cycles of therapy, FDG uptake is moredependent on the tumour regrowth [5]. In HL, the Reed-Sternberg (RS) cells account for less than 1% of the tumour.Bystander, lymphomononuclear cells work, throughcytokines, as an amplifier of the PET detection power. Thesecells are switched off very early (one to two cycles) bychemotherapy [6]. Therefore, the amount of residual activityat interim varies with the kinetics of tumoral destruction, thehistology of lymphoma, the tumoral microenvironment, thetreatment and the time point (two cycles or more) at whichPET is performed. These variations are better described by aquantitative analysis by reference to the baseline PET thanby using a visual dichotomous analysis (positive or negative)which results in a loss of information [3, 5]. In this regard thefive-point scale proposed by Barrington et al. is goingtowards the right direction by giving the possibility to grade

Significance and Regional Dependency of Peptide Transporter (PEPT) 1 in the Intestinal Permeability of Glycylsarcosine: In Situ Single-Pass Perfusion Studies in Wild-Type andPept1Knockout Mice

The purpose of this study was to evaluate the role, relevance, and regional dependence of peptide transporter (PEPT) 1 expression and function in mouse intestines using the model dipeptide glycylsarcosine (GlySar). After isolating specific intestinal segments, in situ single-pass perfusions were performed in wild-type and Pept1 knockout mice. The permeability of [(3)H]GlySar was measured as a function of perfusate pH, dipeptide concentration, potential inhibitors, and intestinal segment, along with PEPT1 mRNA and protein. We found the permeability of GlySar to be saturable (K(m) = 5.7 mM), pH-dependent (maximal value at pH 5.5), and specific for PEPT1; other peptide transporters, such as PHT1 and PHT2, were not involved, as judged by the lack of GlySar inhibition by excess concentrations of histidine. GlySar permeabilities were comparable in the duodenum and jejunum of wild-type mice but were much larger than that in ileum (approximately 2-fold). A PEPT1-mediated permeability was not observed for GlySar in the colon of wild-type mice (<10% residual uptake compared to proximal small intestine). Moreover, GlySar permeabilities were very low and not different in the duodenum, jejunum, ileum, and colon of Pept1 knockout mice. Functional activity of intestinal PEPT1 was confirmed by real-time polymerase chain reaction and immunoblot analyses. Our findings suggest that a loss of PEPT1 activity (e.g., due to polymorphisms, disease, or drug interactions) should have a major effect in reducing the intestinal absorption of di-/tripeptides, peptidomimetics, and peptide-like drugs.

Industrial Sustainability of Competing Wood Energy Options in Canada

The amount of sawmill residue available in Canada to support the emerging cellulosic ethanol industry was examined. A material flow analysis technique was employed to determine the amount of sawmill residue that could possibly be available to the ethanol industry per annum. A combination of two key trends--improved efficiency of lumber recovery and increased uptake of sawmill residues for self-generation and for wood pellet production--have contributed to a declining trend of sawmill residue availability. Approximately 2.3 x 10⁶ bone-dry tons per year of sawmill residue was estimated to be potentially available to the cellulosic ethanol industry in Canada, yielding 350 million liters per year of cellulosic ethanol using best practices. An additional 2.7 billion liters of cellulosic ethanol might be generated from sawmill residue that is currently used for competing wood energy purposes, including wood pellet generation. Continued competition between bioenergy options will reduce the industrial sustainability of the forest industry. Recommendations for policy reforms towards improved industrial sustainability practices are provided.

Fresh and residual phosphorus uptake by ryegrass from soils with different fertilization histories

Organic farming largely depends on animal manure as a source of phosphorus (P) and the recycling of animal manure globally is becoming increasingly important. In a pot experiment, using radioactive P labeling techniques, we studied ryegrass uptake of P applied with animal manure and water soluble mineral fertilizer to soils that had been cropped for 22 years according to organic or conventional farming practices. The soils differed in P status and microbial activity. Labeling soil-available P also allowed assessing the uptake from residual P that remained in the soils because of their different fertilization histories. On each soil, recovery of fresh manure P in four harvests of ryegrass shoots was lower than recovery of mineral P. It ranged from 24% to 35% for manure P and from 37% to 43% for mineral P. Recovery of fresh manure P was affected by soil-available P contents. It was lower at a higher available P in a conventional soil. Different levels in microbial activity among soils were of lesser importance for the recovery of fresh manure P in plants. The recovery of residual P ranged from 9% to 15%. Residual P contained in organic cropped soils contributed less to P nutrition of ryegrass than the residual P contained in conventional cropped soils, probably due to their lower residual P contents being composed of stable P forms. The indirect isotope dilution technique is useful in assessing manure P uptake by plants, but attention must be given to added P interactions, i.e., the potential impact of organic amendments on P uptake from non-labeled soil and residual P.

Clinical usefulness of 99mTc-MIBI scintigraphy in the postsurgical evaluation of patients with differentiated thyroid cancer

Tc-methoxyisobutyl isonitrile (MIBI) has been reported to show considerable clinical utility in the study of many neoplastic diseases. The aim of our study was to investigate the possible role of Tc-MIBI in the initial follow-up of patients with differentiated thyroid cancer (DTC) for detecting residual thyroid uptake and/or loco-regional/distant metastases. Eighty-two patients with DTC (61 women, 21 men; mean age: 49 years) were studied after total or near-total thyroidectomy (not earlier than 3 months after thyroidectomy but before they underwent radioiodine therapy). About 20 min after the intravenous administration of 370 MBq of Tc-MIBI, planar images (and, if necessary, tomographic images, single photon emission tomography) of the cervical and thoracic regions were recorded and compared with posttherapy radioiodine scanning and thyreoglobulin serum levels. MIBI scans detected thyroid remnants in 53 of 82 patients (65%) and metastatic foci in 10 of 11 (91%) patients, in whom a standard activity of 1110 MBq of I administered following MIBI scan had shown the presence of thyroid remnants or metastatic foci, respectively. One metastatic patient was false negative for both MIBI scan and post-I dose whole body scan. Our data indicate that an MIBI scan has a high sensitivity in detecting metastatic lesions from DTC. Therefore, an MIBI scan after thyroidectomy and immediately before radioiodine treatment may be clinically useful for choosing the best therapeutic approach in terms of either ablative or therapeutic I activity for both thyroid remnants and/or DTC metastases and for evaluating surgical reappraisal of metastatic lymph nodes.

The negative effect of some selective insecticides on the functional response of a potential biological control agent, the spider Philodromus cespitum

The impact of five selective insecticides on the functional response of a potential biological control agent, the spider Philodromus cespitum (Walckenaer) (Araneae: Philodromidae), was studied in the laboratory. This spider is the most abundant beneficial arthropod on trees in commercial orchards in central Europe. We expected that selective insecticides applied at the recommended doses would have no effect or a negligible effect on the spiders’ performance. Our results showed that the mortality of spiders resulting from residual uptake of the chemicals differed among insecticides. Dimilin, NeemAzal, Mospilan, and Integro caused mortality of less than 10%, while SpinTor caused mortality of 17%. All five preparations can be considered harmless in terms of mortality in comparison with Decis, which caused 80% mortality. Exposure to residues of NeemAzal, SpinTor, and Dimilin resulted in a significantly lower predation rate than the control. The lowest predation rate was observed in spiders treated with SpinTor. These results imply that the natural pest control provided by P. cespitum spiders can be weakened by the application of SpinTor, NeemAzal, and Dimilin. On the other hand, the functional response was not significantly affected by the application of Integro and Mospilan. Therefore, these two insecticides are recommended for use in the integrated pest management (IPM) of orchards.