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Biomedical subjects

Heikki Minn

Publications and source records attributed to Heikki Minn.

30 records · Page 2Linked to original sources

Use of positron emission tomography with methyl-11C-choline and 2-18F-fluoro-2-deoxy-D-glucose in comparison with magnetic resonance imaging for the assessment of inflammatory proliferation of synovium.

OBJECTIVE: To compare positron emission tomography (PET) and magnetic resonance imaging (MRI) in the evaluation of inflammatory proliferation of synovium. METHODS: Ten patients (mean +/- SD age 36 +/- 13 years) with inflammatory joint disease and with clinical signs of inflammation of the joint were studied. A new tracer for cellular proliferation, methyl-(11)C-choline ((11)C-choline), and a widely used tracer for the detection of inflammation and cancer, 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), were applied for PET imaging, and the results were compared with the findings from gadolinium diethylenetriaminepentaacetic acid-enhanced MR images. The uptake of (11)C-choline and (18)F-FDG in the inflamed synovium was measured and expressed as the standardized uptake value (SUV) and the kinetic influx constant (K(i)) obtained from graphic analysis, and these values were compared with quantitative values on MRI. Synovial volumes were measured on the coronal contrast-enhanced T1-weighted MR images using the standard software of the MR imager. RESULTS: All patients showed high accumulation of both (11)C-choline and (18)F-FDG at the site of arthritic changes, where quantification of the tracer uptake was performed. The SUV of (11)C-choline was 1.5 +/- 0.9 gm/ml (mean +/- SD; n = 10) and the SUV of (18)F-FDG was 1.9 +/- 0.9 gm/ml (n = 10) (P = 0.017). The K(i) of (11)C-choline (mean +/- SD 0.048 +/- 0.042 minute(-1)) was 8-fold higher than the K(i) of (18)F-FDG (0.006 +/- 0.003 minute(-1)) (P = 0.009). Both the uptake of (11)C-choline and the uptake of (18)F-FDG correlated highly with the volume of synovium; the highest correlation was observed with the K(i) of (11)C-choline (r = 0.954, P < 0.0001). CONCLUSION: In the use of PET scans,(11)C-choline can be regarded as a promising tracer for quantitative imaging of proliferative arthritis changes. Nevertheless, subsequent prospective studies with larger numbers of patients are necessary to further characterize the relationship between the findings on PET imaging and the clinical and functional measures of inflammation.

Adult↗

Treatment of squamous cell carcinoma of the oral cavity, oropharynx and hypopharynx--an analysis of 174 patients in south western Finland.

The purpose of this study was to determine the efficacy and feasibility of full-dose preoperative radiation therapy (RT) in head and neck cancer presenting in the oral cavity, oro- and hypopharynx, within a single university hospital district. During a seven-year period, 1989 to 1995, 174 patients with squamous cell carcinoma (SCC) of the oral cavity (OC, 70% of all patients), oropharynx (OP, 15%) and hypopharynx (HP, 15%) were referred to Turku University Central Hospital. All patients were seen by a tumor board consisting of an ENT (ear-nose-throat) head and neck surgeon, a radiation oncologist and a dentist. Potentially curative treatment was given to 142 patients. Of these, 88 (62%) had preoperative RT, 6 (4%) postoperative RT, 34 (24%) definitive RT and 14 patients (10%) were treated with surgery only. The radiation dose was > or = 50 Gy. averagely 64 Gy. The major endpoints of the study were local control, overall survival and major complications of the combined treatment. The 5-year relative survival rate (RSR) was 40% for all, and 43% for patients treated with curative intent. For these, the local control at 5 years was 60%; the disease-specific 5-year survival rate was 65% for the patients with lingual SCC, 45% for those with other oral tumor localizations. 64% for the oropharynx patients and 47% for those with tumor in their hypopharynx, while it was 55% for all patients. The preoperative radiotherapy was fairly well tolerated. Ten (7%) of the patients treated with curative intent suffered major complications, and four patients had evidence of osteoradionecrosis. With the exception of patients with early SCC the outcome remains rather poor in this group of cancer patients who often have marked co-morbidity. In our opinion, preoperative radiotherapy to a dose of 62-64 Gy can safely be given, and remains a feasible means to treat patients with oral, oropharyngeal or hypopharyngeal cancer.

Aged↗

Quantifying tumour hypoxia with fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) and PET using the tumour to plasma ratio.

Fluorine-18 fluoroerythronitroimidazole ([(18)F]FETNIM) is a nitroimidazole compound that is potentially useful as a hypoxia marker in positron emission tomography (PET) studies of oncological patients. Our aim was to develop a simple protocol to quantitate uptake of [(18)F]FETNIM in hypoxic tumours. Dynamic imaging data from ten patients with head and neck cancer undergoing [(18)F]FETNIM PET was used in simulations and model fits to assess hypoxia marker uptake under different levels of blood flow. The distribution volume determined from dynamic PET study was compared with simple tumour to plasma and tumour to muscle ratios at 90-120 min. In skeletal muscle having a low but variable blood flow [2-6 ml/(100 gxmin)], differences in hypoxia-specific uptake of [(18)F]FETNIM remain small and may be hard to detect with PET. At higher blood flow [>20 ml/(100 gxmin)], the retention of [(18)F]FETNIM reflects the oxygenation status well and results in satisfactory contrast between hypoxic and well-oxygenated tissue. A good estimate of tissue hypoxia is accomplished by measuring the tissue to plasma [(18)F]FETNIM activity ratio using only a few late time points. The increased hypoxia-specific retention of [(18)F]FETNIM in tissues with high blood flow, such as malignant tumours, may facilitate application of [(18)F]FETNIM as a hypoxia marker in oncological patients. In the assessment of the tumour to non-target uptake ratio, plasma is the preferred reference tissue rather than muscle, which may show a more heterogeneous tracer uptake not easily controlled for.

Blood Flow Velocity↗

Uptake of [N-methyl-11C]alpha-methylaminoisobutyric acid in untreated head and neck cancer studied by PET.

Amino acid transport system A is expressed strongly in neoplastic cells. [ N-methyl-(11)C]alpha-Methylaminoisobutyric acid ((11)C-MeAIB) is a recently developed tracer for PET studies on system A amino acid transport. (11)C-MeAIB is a metabolically stable amino acid analogue which is transported from plasma into the tissue by system A. This study evaluated the kinetics of (11)C-MeAIB uptake from plasma into tumour tissue and normal tissues in 13 patients with untreated head and neck cancer. (11)C-MeAIB uptake in tumour was compared with histological grade and proliferative activity. Tracer uptake was quantitated by calculating the standardised uptake values (SUVs) and the kinetic influx constants ( K(i)) using graphical analysis. All tumours accumulated (11)C-MeAIB and were visualised clearly. In the graphical analysis, linear plots were achieved; the mean K(i) value of tumour was 0.056+/-0.026 min(-1), and the mean SUV was 6.1+/-2.7. A close correlation between graphically obtained K(i) and semi-quantitative SUV in tumours was found ( r=0.887, P=0.00005). We could not demonstrate a correlation between the uptake of (11)C-MeAIB and the grade of malignancy or the proliferative index, as assessed using Ki-67 immunohistochemical assay. Head and neck cancer can be effectively imaged with (11)C-MeAIB PET. (11)C-MeAIB showed active and rapid transport into tumour tissue and salivary glands. Further studies on the applicability of (11)C-MeAIB PET for radiation treatment planning in the head and neck region and the regulation of system A amino acid transport under different metabolic states are warranted.

Adult↗

Metabolic characterization of childhood brain tumors: comparison of 18F-fluorodeoxyglucose and 11C-methionine positron emission tomography.

BACKGROUND: Positron emission tomography (PET) scans of primary brain tumors were performed in pediatric patients to examine whether metabolic characteristics could be used as an index of clinical aggressiveness. METHODS: Twenty-seven pediatric patients with untreated primary central nervous system neoplasms were studied with PET scans using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) and/or L-[methyl-(11)C] methionine (MET). Metabolic characteristics as assessed with FDG and MET standardized uptake values (SUV) and SUV-to-normal brain ratios were compared with histopathology and selected histochemical features such as proliferation activity (Ki-67(MIB-1)) and apoptotic, vascular, and cell density indices. The median followup time was 43 months. RESULTS: The accumulation of both FDG and MET was significantly higher in high-grade than in low-grade tumors, but a considerable overlap was found. The accumulation of both tracers was associated positively with age. High-grade tumors showed higher proliferative activity and vascularity than the low-grade tumors. In univariate analysis, FDG-PET, MET-PET, and apoptotic index were independent predictors of event-free survival. CONCLUSION: We found that both FDG and MET uptake in pediatric brain tumors are associated with malignancy grade. However, no clear limits of SUVs and SUV-to-normal brain ratios can be set between low-grade and high-grade tumors, which makes the assessment of malignancy grade using metabolic imaging with PET scan difficult in individual cases. Although FDG-PET and MET-PET do not compensate for histopathologic evaluation, they may give valuable additional information especially if invasive procedures to obtain histopathologic samples are not feasible.

Adolescent↗

The effects of irradiation and hyperbaric oxygen on bone formation during rabbit mandibular distraction.

[18F-]fluoride positron-emission tomography (PET) was used to assess bone formation during mandibular distraction osteogenesis. There were three study groups: irradiation, irradiation+hyperbaric oxygen and control. The two experimental groups received a tumoricidal dose of irradiation to the mandible, and one group was also given hyperbaric oxygen (2.5 ATA (atmospheres absolute) for 90 min) 18 times preoperatively. Control animals received neither irradiation nor oxygen. A unilateral osteotomy was made and, after a period of latency, bone distraction was started, continued for 2 weeks, and the distraction generated was then allowed to consolidate for 4 weeks. The first PET study was performed at the end of distraction and the second at the end of consolidation. At the end of distraction, the metabolic activity of bone in the distracted area was significantly higher in the controls than in either experimental group; differences between the experimental groups were not statistically significant. By the end of consolidation, activity in the control group had diminished to the same as in the two experimental groups, in which no significant change had occurred. Radioactivity was still significantly higher at second imaging on the distracted than non-distracted side in the control and irradiation+hyperbaric oxygen groups, but not in the group that was only irradiated. The results indicate that previous irradiation disturbs bone formation during mandibular distraction osteogenesis. Hyperbaric oxygen was not able to prevent the suppression of osteogenesis caused by radiotherapy but it might improve bone formation by prolonging high osteogenic activity.

Animals↗

Combined external and intraluminal radiotherapy in the treatment of advanced oesophageal cancer.

BACKGROUND AND PURPOSE: Oesophageal cancer still has a dismal prognosis. Radical surgery is by far the most successful treatment but most patients are not operable at the time of diagnosis and for these patients external beam radiotherapy with or without concurrent chemotherapy offers the best choice for cure or palliation. In patients with advanced oesophageal cancer, intraluminal brachytherapy has been proposed as a complementary method to increase local control. PATIENTS AND METHODS: Between 1989 and 1999, 40 patients with inoperable oesophageal cancer were treated with combined external and intraluminal radiation therapy in Turku University Central Hospital. The external radiation was performed with a median total dose of 40 Gy given in 20 fractions. On the average a week after the external radiation a median total dose of 10 Gy intraluminal radiation therapy was given in 4 fractions. RESULTS: The intraluminal brachytherapy could be performed without technical difficulties and no major complications were seen. In many cases (16 out of 40 patients, 40%), the symptoms could be relieved immediately and in most cases the progression of the disease could be delayed as evidenced by post-treatment serial endoscopy. No major complications were encountered. The 1- and 2-year survival rates were 30 and 17.5%, respectively. All patients alive at 2 years can be considered as long-term survivors. Median follow-up was 86 months. CONCLUSIONS: Intraluminal brachytherapy is a safe and efficient treatment modality which offers a potential means of cure for selected patients with oesophageal cancer.

Aged↗

Reproducibility of common semi-quantitative parameters for evaluating lung cancer glucose metabolism with positron emission tomography using 2-deoxy-2-[18F]fluoro-D-glucose.

PURPOSE: Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been used for various cancers, but reproducibility of common utilized semi-quantitative parameters, such as the maximal single pixel standardized uptake value (SUV) and effective glycolytic volume (EGV), remains unknown. Knowledge of precision is essential for applying these parameters to treatment monitoring. The purpose of this investigation was to assess the precision of PET results obtained by repeated examinations of patients with untreated lung cancer. PATIENTS AND METHODS: Ten patients with lung cancer underwent two PET examinations within a week with no intervening treatment. The reproducibility of three parameters:((1) maximal SUV of 1 x 1 pixel anywhere in the tumor, calculated on the basis of predicted lean body mass [SULmax]; (2) highest average SUV at 4 x 4 pixels in the tumor adjusted by predicted lean body mass [SULmean]; and (3) EGV calculated by multiplying SUL by tumor volume), using PET images obtained at 50-60 min post-injection, were examined. Plasma glucose, insulin and free fatty acid levels were also monitored. RESULTS: The SULmax, SULmean, and EGV were measured with a mean +/- S.D. difference of 11.3% +/- 8.0, 10.1% +/- 8.2, and 10.1% +/- 8.0%, respectively. By multiplying SUL by plasma glucose concentration, the mean differences were slightly reduced to 7.2% +/- 5.8, 6.7% +/- 6.2, and 9.5% +/- 8.2, respectively. CONCLUSION: These data indicate that commonly used semi-quantitative indices of glucose metabolism on PET show high reproducibly. This supports their use in sequential quantitative analysis in PET, such as in treatment response monitoring.

Journal Article↗

18F-Fluoroerythronitroimidazole radiation dosimetry in cancer studies.

UNLABELLED: 18F-Fluoroerythronitromidazole (FETNIM) is a new promising PET tracer for imaging tumor hypoxia. Accurate radiation dosimetry is important for estimating absorbed radiation doses to patients and for calculating the allowable injected dose. METHODS: Radiation absorbed doses were estimated from PET scans obtained on cancer patients on the basis of the MIRD procedure. Dynamic acquisition data was obtained from the thorax, abdomen, and head and neck regions. The tracer was injected intravenously and mean injected activity was 366 MBq (range, 288-385 MBq). Arterial blood was continuously assayed over dynamic PET imaging. The bladder wall dose was evaluated from the voided urine activity measurements. RESULTS: The effective dose to a 70-kg adult was 0.015 or 0.019 mSv/MBq, calculated on 2- or 4-h voiding intervals, respectively. The critical organ proved to be the urinary bladder wall, with a highest absorbed dose of 0.062 or 0.127 mGy/MBq depending on the voiding schedule as described above. Absorbed doses in all other organs were at least 5-fold smaller than the bladder wall doses. CONCLUSION: With an injected activity of 370 MBq (18)F-FETNIM, the radiation doses are generally comparable with those of other related radionuclide imaging procedures. Specifically, in comparison with (18)F-fluoromisonidazole, the absorbed doses of (18)F-FETNIM are equal. However, special attention should be given to adequate hydration and voiding to limit the relatively high exposure of the critical organ, bladder wall, to (18)F-FETNIM.

Female↗

Boron neutron capture therapy of brain tumors: clinical trials at the finnish facility using boronophenylalanine.

Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400 mg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61 Gy (W), and the average normal brain dose from 3 to 6 Gy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50-60 Gy, were treated with BPA-based BNCT using the BPA dosage of 290 mg/kg. The average planning target dose in these patients was 25-29 Gy (W), and the average whole brain dose 2-3 Gy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photon radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.

Adult↗