M. P. M. Stokkel

Positron-emission tomography with [18F]fluorodeoxyglucose. Part I. Biochemical uptake mechanism and its implication for clinical studies.

Abstract Over the past decades, Positron Emission Tomography has opened a new field of imaging. Nowadays, this technique is being used for diagnosing, staging disease as well as for prognostic stratification and monitoring therapy. In this respect, [18F]fluorodeoxyglucose (FdGlc) is by far the most commonly used PET agent. Many factors have been identified being responsible for a high uptake of this agent in malignancy. However, additional factors such as tumour treatment may interfere with the uptake mechanism. Knowledge of all these factors is a prerequisite for an optimal interpretation of PET studies and, consequently, for a reliable judgement of tumour status. In this article, a review is given of the factors influencing FdGlc uptake and the implications for clinical studies.

Positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose in oncology. Part II. The clinical value in detecting and staging primary tumours.

Abstract The tumoral uptake of 2-[18F]fluoro-2-deoxy-D-glucose (18FdGlc) is based upon enhanced glycolysis. Positron-emission tomography (PET) using 18FdGlc provides the physiological and metabolic information. 18FdGlc PET has been used successfully for assessing primary tumours and metastases, prognosis, and planning and for monitoring tumour therapy as well as for early detection of recurrent tumour growth. This review summarises the uptake mechanism of 18FdGlc in benign and malignant lesions, its relation to histolopathology, and its clinical value for detecting and staging primary tumours.

Positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose in oncology

Abstract Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in breast cancer, lymphomas and gliomas. It is found that the amount of FDG uptake strongly correlates with response to therapy in breast cancer, lymphomas, and gliomas; a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small patient numbers, whereas the exact response mechanism is still unknown. Therefore, more studies in comparable patient groups are required to achieve a better understanding of FDG uptake patterns after therapy. Part IIIb deals with lung, and head and neck cancer, hepatocellular and colorectal tumours, and sarcoma.

The clinical value of 18F-FDG detection with a dual-head coincidence camera: a review

Abstract. Positron emission tomography (PET) has evolved into a technique that can accurately determine the distribution of positron-emitting radionuclides. The addition of a coincidence detection mode to a standard dual-head detector system has resulted in the option of single-photon and annihilation coincidence detection. This new device for imaging fluorine-18 2-fluoro-2-deoxy-D-glucose (18F-FDG) accumulation in neoplasms became commercially available in 1994. Besides conventional low-energy imaging in the collimated single-photon mode, it offers a relatively inexpensive opportunity to perform uncollimated PET by switching to the coincidence acquisition mode. This review summarises the clinical value of 18F-FDG detection with a dual-head coincidence camera in oncology. The results are compared with the overall results obtained using dedicated PET scanners. With respect to head and neck tumours, 18F-FDG coincidence mode gamma camera imaging (CGI) yields results that are in agreement with those obtained with dedicated PET scanners. With regard to other malignancies, such as lung cancer, lymphoma and brain tumours, data in the literature are too scarce to draw any definite conclusions. In general, the results of 18F-FDG CGI in tumours >15xa0mm seem to be comparable to those obtained with dedicated PET scanners, whereas in tumours <15xa0mm, the relative sensitivity of 18F-FDG CGI is approximately 80%. Using attenuation correction, the diagnostic yield of 18F-FDG CGI may increase. However, further clinical investigation is required to definitely establish its value in staging primary disease, therapy monitoring and assessment of tumour recurrence in clinical oncology.

The value of quantitative gallium-67 single-photon emission tomography in the clinical management of malignant external otitis

Abstract.Malignant external otitis (MEO) is a severe infectious disorder usually caused by Pseudomonas aeruginosa, which most frequently affects diabetic patients. Due to its rarity, the diagnosis of MEO is often not made promptly. Extension into deeper structures or chronic osteomyelitis may occur without signs of infection on local clinical examination. Of the imaging techniques, magnetic resonance imaging provides a fairly adequate picture of the spread of the disease, but, as with computed tomography (CT) scanning and bone scintigraphy, the images remain unchanged for a long time after disease regression. The objective of this study was to establish whether quantitative gallium-67 single-photon emission tomography (SPET) represents an accurate method for the assessment of infection and, moreover, for the monitoring of therapeutic effect. Eight patients (five males, three females) with the clinical diagnosis of MEO were studied. In three patients antibiotic treatment was prolonged for several weeks because visual analysis of gallium scintigraphy still showed slightly increased uptake in the affected area on the first follow-up scan. In one patient, it was decided to stop antibiotic treatment despite a slight increase in uptake on the second follow-up scan. Lesion to non-lesion (L/NL) ratios obtained from 67Ga SPET images at initial diagnosis and during follow-up were assessed in correlation with clinical and biochemical data and with the results of CT scans. In addition to a raised erythrocyte sedimentation rate (ESR), all patients showed increased uptake on the affected side, with L/NL ratios ranging from 1.4 to 3.6 at the time of diagnosis. CT scans failed to demonstrate abnormalities in four patients. Including four scans demonstrating slightly increased uptake in the affected area, L/NL ratios after 6–8 weeks of antibiotic treatment were 1.0±0.1. Despite a persistently elevated ESR in the majority of patients, none of them demonstrated local recurrence or complications during follow-up. In all patients, leucocyte count was within the normal range throughout the course. No relation was found between the slightly increased uptake on the follow-up scans and surgical treatment. It is concluded that in addition to the visual analysis of 67Ga SPET imaging, L/NL ratios should be calculated for a more accurate assessment of disease activity in MEO. Despite visually slightly increased uptake, L/NL ratios of 1.0±0.1 during follow-up are highly indicative of complete recovery, regardless of ESR values or leucocytosis. CT scans are of little value for diagnosis or for monitoring of therapeutic effect.

Positron emission tomography: a technical introduction for clinicians.

Up to a few years ago, positron emission tomography (PET) was known as a very expensive research tool using positron emitting radiopharmaceuticals to study metabolic processes in vivo. Recent developments in detector technology enabled the detection of the distribution of positron emitting radionuclides inside the human body through dual-headed gamma camera systems. These much cheaper cameras did move the focus of PET from research to clinical applications. The improved availability of [(18)F]fluorodeoxyglucose has promoted clinical PET. Ongoing developments in detector and image reconstruction technology may lead to even more accurate imaging in the clinical setting. New applications in diagnosing and staging of cancer patients came across and more will arise. In this paper, we present a short historical overview and a technical introduction of PET.

Cutaneous malignant melanoma: clinical aspects, imaging modalities and treatment

Abstract. Cutaneous melanoma is a highly malignant tumour of the melanocytes presenting characteristic metabolic and biological features. Early detection decreases mortality and morbidity and provides the best chance for optimal clinical management. Imaging techniques, including scintigraphy, have assumed an important role in detection strategies. As a functional modality, nuclear medicine offers a variety of possibilities to assist in the clinical management of malignant melanoma. This review discusses the clinical aspects and treatment of melanoma, and the imaging techniques used for its diagnosis, staging and follow-up. A survey of currently available techniques is presented.

APC mutations are associated with increased bone mineral density in patients with familial adenomatous polyposis

The canonical Wnt pathway plays a key regulatory role in osteoblastogenesis and bone mass acquisition through its main effector, β‐catenin. Adenomatous polyposis coli (APC) represents the key intracellular gatekeeper of β‐catenin turnover, and heterozygous germ‐line mutations in the APC gene cause familial adenomatous polyposis (FAP). Whether APC mutations affect bone mass has not been previously investigated. We conducted a cross‐sectional study evaluating skeletal status in FAP patients with a documented APC mutation. Twenty‐two FAP patients with a mean age of 42 years (54.5% women) were included in this study. Mean bone mineral density (BMD) Z‐scores were significantly increased above normal at all measured sites: lumbar spine (pu2009<u2009.01), total hip (pu2009<u2009.01), femoral neck (pu2009<u2009.05), and trochanter (pu2009<u2009.01). Z‐scores were +1 or greater in 14 patients (63.6%) and +2 or greater in 5 (22.7%). Mean values of bone turnover markers were within normal ranges. There was a significant positive correlation between procollagen type I N‐terminal propeptide (P1NP) and β‐crosslaps (β‐CTX) (ru2009=u20090.70, pu2009<u2009.001) and between these markers and sclerostin and BMD measurements. We demonstrate that FAP patients display a significantly higher than normal mean BMD compared with age‐ and sex‐matched healthy controls in the presence of a balanced bone turnover. Our data suggest a state of “controlled” activation of the Wnt signaling pathway in heterozygous carriers of APC mutations, most likely owing to upregulation of cytoplasmic β‐catenin levels.

Scintigraphic head-to-head comparison between 99mTc-WBCs and 99mTc-LeukoScan in the evaluation of inflammatory bowel disease: a pilot study.

Abstract Scintigraphy with technetium-99m labelled white blood cells (WBCs) is routinely used in our hospital for the assessment of inflammatory bowel disease (IBD). The main disadvantages of this diagnostic tool are its time-consuming nature and the handling of blood itself. 99mTc-LeukoScan is a relatively new, easily prepared agent that is used for the detection of osteomyelitis. To assess its value in IBD, a scintigraphic head-to-head comparison was performed between 99mTc-LeukoScan and 99mTc-WBCs. 99mTc-LeukoScan scintigraphy was performed in six patients with clinically active IBD and increased uptake on 99mTc-WBC images. The interval between the scintigraphic studies ranged from 2 to 7 days, and endoscopy was subsequently performed to confirm active IBD. In three out of six patients with increased uptake on the 99mTc-WBC scans, 99mTc-LeukoScan images showed very discreet activity in the bowel, but the sites did not correspond with the inflammation sites seen on 99mTc-WBC scintigraphy and found at endoscopy. In the other three patients, 99mTc-LeukoScan scintigraphy revealed a physiological distribution but no abnormalities. In conclusion, 99mTc-LeukoScan is not an alternative agent for the assessment of IBD. A prospective study is not justified owing to the false-negative results.

Pretreatment serum lactate dehydrogenase as additional staging parameter in patients with small-cell lung carcinoma

Purpose: At present the standard staging procedure in patients with small-cell lung cancer (SCLC) is extensive, expensive and time-consuming. Furthermore, the predictive and prognostic value of the current staging system is poor. To determine the value of pretreatment clinical and biochemical parameters to predict tumour stage and to assess prognosis, a retrospective study was performed of 121 consecutive patients with newly diagnosed SCLC. Methods: On the basis of routine diagnostic procedures, 51 patients were staged as having limited disease and 70 patients as having extensive disease. During follow-up, data on tumour progression and survival were gathered. These data and the tumour stage were correlated with lactate dehydrogenase (LDH), alkaline phosphatase, liver enzymes, leucocyte count, protein, albumin, calcium, age and gender. Results: Follow-up ranged from 1u2009week to 96u2009months, during which 110u2009patients died. In all patients with LDH levels above 400u2009U/l (nu2009=u200931), metastases were found at the initial stage, whereas all patients initially staged as having limited disease and LDH levels above 240u2009U/l showed tumour progression. Bone and liver were found to be the most commonly involved sites, whereas the incidence of brain metastases increased during follow-up. In patients initially staged as having limited disease, no differences in survival were found between those showing local recurrence and those developing metastases during follow-up (Pu2009=u20090.67). Compared to the patients initially staged as having extensive disease, the survival of both groups was significantly better (Pu2009<u20090.001). Significant independent variables of survival were LDH, albumin, initial stage and gender, but LDH was the best overall predictor (Pu2009<u20090.001). Conclusion: These results suggest that pretreatment LDH may be used as an additional staging parameter in SCLC, which can identify prognostic subgroups before treatment.