Journal - Der Radiologe (Germany )

Abstract :

Adenocarcinomas of the pancreas represent the majority (>95%) of all malignant pancreatic tumors. They are formed from malignant degeneration of the exocrine part of the pancreas. Cystic acinar tumors are much rarer and originate from secretion-producing parenchymal cells of the pancreas. Endocrine tumors of the pancreas will not be dealt with in this context.

Journal - Journal of nuclear medicine : official publication, Society of Nuclear Medicine (United States )

Abstract :

Resistance to radiotherapy or chemotherapy is a common cause of treatment failure in high-risk leukemias. We evaluated whether selective nanoirradiation of DNA with Auger electrons emitted by 5-(123)I-iodo-4'-thio-2'-deoxyuridine ((123)I-ITdU) can induce cell kill and break resistance to doxorubicin, beta-, and gamma-irradiation in leukemia cells. METHODS: 4'-thio-2'-deoxyuridine was radiolabeled with (123/131)I and purified by high-performance liquid chromatography. Cellular uptake, metabolic stability, DNA incorporation of (123)I-ITdU, and the effect of the thymidylate synthase (TS) inhibitor 5-fluoro-2'-deoxyuridine (FdUrd) were determined in HL60 leukemia cells. DNA damage was assessed with the comet assay and quantified by the olive tail moment. Apoptosis induction and irradiation-induced apoptosis inhibition by benzoylcarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD.fmk) were analyzed in leukemia cells using flow cytometry analysis. RESULTS: The radiochemical purity of ITdU was 95%. Specific activities were 900 GBq/micromol for (123)I-ITdU and 200 GBq/micromol for (131)I-ITdU. An in vitro cell metabolism study of (123)I-ITdU with wild-type HL60 cells demonstrated an uptake of 1.5% of the initial activity/10(6) cells of (123)I-ITdU. Ninety percent of absorbed activity from (123)I-ITdU in HL60 cells was specifically incorporated into DNA. (123)I-ITdU caused extensive DNA damage (olive tail moment > 12) and induced more than 90% apoptosis in wild-type HL60 cells. The broad-spectrum inhibitor of caspases zVAD-fmk reduced (123)I-ITdU-induced apoptosis from more than 90% to less than 10%, demonstrating that caspases were central for (123)I-ITdU-induced cell death. Inhibition of TS with FdUrd increased DNA uptake of (123)I-ITdU 18-fold and the efficiency of cell kill about 20-fold. In addition, (123)I-ITdU induced comparable apoptotic cell death (>90%) in sensitive parental leukemia cells and in leukemia cells resistant to beta-irradiation, gamma-irradiation, or doxorubicin at activities of 1.2, 4.1, 12.4, and 41.3 MBq/mL after 72 h. This finding indicates that (123)I-ITdU breaks resistance to beta-irradiation, gamma-irradiation, and doxorubicin in leukemia cells. CONCLUSION: (123)I-ITdU-mediated nanoirradiation of DNA efficiently induced apoptosis in sensitive and resistant leukemia cells against doxorubicin, beta-irradiation, and gamma-irradiation and may provide a novel treatment strategy for overcoming resistance to conventional radiotherapy or chemotherapy in leukemia. Cellular uptake and cell kill are highly amplified by inhibiting TS with FdUrd.

Journal - European journal of nuclear medicine and molecular imaging (Germany )

Abstract :

PURPOSE: The aim of this study was to assess the accuracy and clinical impact of [(11)C]choline PET/CT for localizing occult relapse of prostate adenocarcinoma after radical prostatectomy. METHODS: Fourty-nine patients with prostate adenocarcinoma, radical prostatectomy, no evidence of metastatic disease, and occult relapse underwent [(11)C]choline PET/CT. Thirty-six of the patients had biochemical evidence and histological evaluation of local recurrence. Thirteen patients had PSA < 0.3 ng/ml and no evidence of active disease after 1 year follow-up. Focal nodular [(11)C]choline uptake in the prostatic fossa was visually assessed and graded on a five point scale. Maximum standardized radioactivity uptake value (SUV(max)) and the lesion size were measured. A receiver operating characteristic (ROC) analysis was performed and the clinical impact of the PET/CT study was determined. RESULTS: [(11)C]choline PET/CT was true positive in 23/33 patients and true negative in 12/13 controls. SUV(max) of local recurrence was 3.0 (median, range 0.6-7.4) and 1.1 (0.4-1.6) in controls (p = 0.0002). Lesion size was 1.7 cm (range 0.9-3.7). Area under the ROC curve for detecting relapse was 0.90 +/- 0.05 and 0.83 +/- 0.06 for visual evaluation and SUV(max), respectively. Sensitivity and specificity of [(11)C]choline PET/CT were 0.73 and 0.88, respectively. [(11)C]choline PET/CT identified 12/17 (71%) patients with a favourable biochemical response to local radiotherapy at 2 year (median, 0.8-3.2 range) follow-up. CONCLUSIONS: Focally increased [(11)C]choline uptake in the prostatic bed reliably predicted local low volume occult relapsing prostate adenocarcinoma after radical prostatectomy and identified 71% of patients with a favourable biochemical response to local radiotherapy.

Journal - Der Urologe. Ausg. A (Germany )

Abstract :

Prostate carcinoma is the most common life-threatening cancer affecting men in the western world. In Germany about 40,600 new cases have to be expected each year. The mortality is around 10%. The major goals of pretherapeutic imaging are to determine the local extent of prostate carcinoma in terms of intraprostate localisation, extracapsular extension (ECE), seminal vesicle invasion (SVI), tumour infiltration into neurovascular bundles, and if this has taken place, into surrounding tissues and organs in the small pelvis, detection of loco-regional metastases via the lymph nodes and of this so, of distant metastases. Exact pretherapeutic diagnosis and staging are essential, because the tumour treatment must be selected in strict dependence on clinical tumour stage and risk profile.Both anatomic and functional molecular imaging of prostate carcinoma have advanced significantly in recent years. When there are problems with diagnosis, e.g. when prostate punch biopsies are negative while the suspicion of prostate carcinoma persists, C-11/F-18 choline PET/CT and MRT/MRS may be helpful in localising the carcinoma, revealing how the carcinoma relates to the surrounding intra- and extraprostatic structures and organs, and making a targeted repeat biopsy possible. Lymphotropic contrast agents are highly promising for accurate nodal staging of prostate carcinoma, but are not yet available for routine clinical use; In these circumstances, the sensitivity of nodal staging with the widely available imaging modalities remains inadequate, and its specificity is also less than optimal. There has been particularly substantial progress in the localisation of local relapse, which can be imaged with contrast-enhanced C-11-choline PET/CT and MRT in most cases when PSA is >0.5-1 ng/ml. 18F-Fluoride PET/CT has proved accurate in the diagnosis of skeletal metastases from prostate carcinoma.

Journal - Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer (Germany )

Journal - European journal of nuclear medicine and molecular imaging (Germany )

Abstract :

3'-Deoxy-3'-(18)F-fluorothymidine (FLT) was developed in 1998 by Shields and co-workers because monitoring of treatment response would be facilitated by imaging agents able to provide measures of tissue and tumour proliferation. Since then, FLT metabolism has been clarified in more detail in cell culture and experimental animal tumour models and also in clinical studies. Recently, FLT has increasingly been used for the assessment of response to anticancer treatment, mainly in tumour xenograft SCID mouse models; in contrast, clinical data are scarce. In this article we briefly summarise the intermediary metabolism of FLT and its application as an anticancer treatment response probe. The potential value and limitations of FLT as a highly promising proliferation imaging probe and its use for monitoring of treatment response are discussed.

Journal - Der Urologe. Ausg. A

Abstract :

Functional imaging of prostate carcinoma was examined with the metabolic substrates 2-(18)F-fluorodeoxyglucose, (11)C-methionine, (18)F-fluorodihydrotestosterone, (11)C-acetate and (11)C/(18)F-choline. Based on upregulated enzymes of phospholipid metabolism in prostate carcinoma, (11)C/(18)F-choline is preferentially incorporated into phosphatidylcholine of membrane lipids of prostate cancer cells. PET allows sensitive detection of the (11)C/(18)F-choline signal and PET/CT fusion imaging enables intraprostatic signal localisation. Most published studies report a high detection rate of prostate carcinoma with (11)C/(18)F-choline PET/CT. Differentiation of prostate carcinoma from benign hyperplasia and from focal chronic prostatitis may be difficult; acute prostatitis accumulates (11)C/(18)F-choline with an intensity comparable to prostate carcinoma.

Journal - Der Urologe. Ausg. A (Germany )

Abstract :

Functional imaging of prostate carcinoma was examined with the metabolic substrates 2-(18)F-fluorodeoxyglucose, (11)C-methionine, (18)F-fluorodihydrotestosterone, (11)C-acetate and (11)C/(18)F-choline. Based on upregulated enzymes of phospholipid metabolism in prostate carcinoma, (11)C/(18)F-choline is preferentially incorporated into phosphatidylcholine of membrane lipids of prostate cancer cells. PET allows sensitive detection of the (11)C/(18)F-choline signal and PET/CT fusion imaging enables intraprostatic signal localisation. Most published studies report a high detection rate of prostate carcinoma with (11)C/(18)F-choline PET/CT. Differentiation of prostate carcinoma from benign hyperplasia and from focal chronic prostatitis may be difficult; acute prostatitis accumulates (11)C/(18)F-choline with an intensity comparable to prostate carcinoma.

Journal - Journal of nuclear medicine : official publication, Society of Nuclear Medicine (United States )

Abstract :

The ability of 11C-choline and multimodality fusion imaging with integrated PET and contrast-enhanced CT (PET/CT) was investigated to delineate prostate carcinoma (PCa) within the prostate and to differentiate cancer tissue from normal prostate, benign prostate hyperplasia, and focal chronic prostatitis. METHODS: All patients with PCa gave written informed consent. Twenty-six patients with clinical stage T1, T2, or T3 and biopsy-proven PCa underwent 11C-choline PET/CT after intravenous injection of 1,112 +/- 131 MBq 11C-choline, radical retropubic prostatovesiculectomy, and standardized prostate tissue sampling. Maximal standardized uptake values (SUVs) of 11C-choline within 36 segments of the prostate were determined. PET/CT results were correlated with histopathologic results, prostate-specific antigen (PSA), Gleason score, and pT stage. RESULTS: The SUV of 11C-choline in PCa tissue was 3.5 +/- 1.3 (mean +/- SD) and significantly higher than that in prostate tissue with benign histopathologic lesions (2.0 +/- 0.6; P < 0.001 benign histopathology vs. cancer). Visual and quantitative analyses of segmental 11C-choline uptake of each patient unambiguously located PCa in 26 of 26 patients and 25 of 26 patients, respectively. A threshold SUV of 2.65 yielded an area under the receiver-operating-characteristic (ROC) curve of 0.89 +/- 0.01 for correctly locating PCa. The maximal 11C-choline SUV did not correlate significantly with PSA or Gleason score but did correlate with T stage (P = 0.01; Spearman r = 0.49). CONCLUSION: 11C-Choline PET/CT can accurately detect and locate major areas with PCa and differentiate segments with PCa from those with benign hyperplasia, chronic prostatitis, or normal prostate tissue. The maximal tumoral 11C-choline uptake is related to pT stage.

Journal - Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology (UNITED STATES )

Abstract :

Iodine 123-labeled iodophenylpentadecanoic acid (IPPA) has been synthesized for investigating myocardial free fatty acid (FFA) metabolism. The diagnostic application of labeled FFA in heart disease may be important, because FFA is the preferred substrate of cardiac energy metabolism at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with beta-oxidation, which is extremely sensitive to oxygen deprivation. This article outlines basic physiologic pathways of cardiac IPPA metabolism in normal, acutely ischemic, and reperfused viable myocardium and summarizes the results of experimental studies in animals, validating the application of IPPA as an 123I-labeled fatty acid analog. In addition, the most important clinical studies indicating the clinical use of IPPA for diagnosis of coronary heart disease and myocardial viability are presented.

Journal - European journal of nuclear medicine (GERMANY )

Abstract :

Interest in bone marrow scanning has been renewed as the result of the development of radiopharmaceuticals for evaluating specific aspects of bone marrow anatomy, physiology and pathology. This article provides a brief review of bone marrow structure, blood flow and function essential to the understanding of basic principles of bone marrow radionuclide imaging. The prospects and limitations of imaging haematopoietic bone marrow in man using indium 111 chloride, technetium-99m (99mTc)-labelled microcolloid or 99mTc-labelled monoclonal antigranulocytic and antimyelocytic antibodies are discussed in more detail. The technical aspects of bone marrow scintigraphy are presented. Results of more recent studies evaluating bone marrow scanning in circulatory, inflammatory and in systemic haematological disorders are summarized. Special attention is paid to the concept of bone marrow micrometastases and its implications for the follow-up of patients with malignant tumours. Recent results suggest that immunoscintigraphy of bone marrow may provide a novel and sensitive approach for establishing the presence and extent of bone marrow infiltration.