Cardiac shockwave therapy in patients with chronic refractory angina pectoris.

BACKGROUND: Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT. METHODS: We included 33 patients (mean age 70 ± 7 years, mean left ventricular ejection fraction 55 ± 12 %) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3-7 spots/session, 100 impulses/spot, 0.09 mJ/mm(2)) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session. RESULTS: One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p < 0.01) and the angina symptoms diminished from CCS class III to CCS class II (p < 0.01). This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy (54.2 ± 7.7 % to 56.4 ± 9.4 %, p = 0.016) and by increased exercise tolerance at 4-month follow-up (from 7.4 ± 2.8 to 8.8 ± 3.6 min p = 0.015). No clinically relevant side effects were observed. CONCLUSION: CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects. The study provides a solid basis for a randomised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease.

Low brown adipose tissue activity in endurance-trained compared with lean sedentary men.

BACKGROUND/OBJECTIVES: It has now been unequivocally demonstrated that humans possess functional brown adipose tissue (BAT) and that human BAT can be recruited upon chronic cold stimulation. Recruitment of BAT has been postulated as a potential strategy to counteract the current global obesity epidemic. Recently, it was shown in rodents that endurance exercise training could stimulate the recruitment of brown-like adipocytes within white adipose tissue (WAT) via exercise-induced myokines such as irisin (the cleaved circulating product of the type 1 membrane protein FNDC5) and interleukin-6 (IL-6). Our objective was to test whether endurance-trained athletes had increased cold-stimulated BAT activity and browning of subcutaneous WAT compared with lean sedentary males. SUBJECTS/METHODS: Twelve endurance-trained athletes and 12 lean sedentary males were measured during 2 h of mild cold exposure to determine cold-induced BAT activity via [(18)F]fluorodeoxyglucose-positron emission tomography-computed tomography ([(18)F]FDG-PET-CT) scanning. Skeletal muscle FNDC5 expression, as well as plasma irisin and IL-6 levels were determined. In addition, a subcutaneous abdominal WAT biopsy was taken to measure gene expression of several markers for browning of WAT. RESULTS: Cold-induced BAT activity was significantly lower in athletes, and no differences in gene expression of classical brown and beige adipocyte markers were detected in subcutaneous WAT between the groups. As expected, mRNA expression of FNDC5 in skeletal muscle was significantly higher in endurance athletes but plasma irisin and Il-6 levels were similar in both groups. CONCLUSIONS: These results indicate that chronic endurance exercise is not associated with brown and beige adipocyte recruitment; in fact endurance training appears to be linked to lower the metabolic activity of BAT in humans.

Increase in brown adipose tissue activity after weight loss in morbidly obese subjects.

CONTEXT: Stimulation of thermogenesis in brown adipose tissue (BAT) is a potential target to treat obesity. We earlier demonstrated that BAT activity is relatively low in obese subjects. It is unknown whether BAT can be recruited in adult humans. OBJECTIVE: To study the dynamics of BAT, we observed BAT activity in morbidly obese subjects before and after weight loss induced by bariatric surgery. DESIGN: This was an observational prospective cohort study. SETTING: The study was conducted at a referral center. PATIENTS: Ten morbidly obese subjects eligible for laparoscopic adjustable gastric banding surgery were studied before and 1 yr after bariatric surgery. MAIN OUTCOME MEASURE: The main outcome measure was BAT activity, as determined after acute cold stimulation using (18)F-fluorodeoxyglucose positron emission tomography and computed tomography. RESULTS: Before surgery, only two of 10 subjects showed active BAT. One year after surgery, the number of subjects with active BAT was increased to five. After weight loss, BAT-positive subjects had significantly higher nonshivering thermogenesis compared with BAT-negative subjects (P < 0.05). CONCLUSIONS: The results show that in humans BAT can be recruited in the regions in which it was also reported in lean subjects before. These results for the first time show recruitment of BAT in humans and may open the door for BAT-targeted treatments of obesity.

Selective internal radiation therapy (SIRT) in primary or secondary liver cancer.

Most patients with a history of common solid tumors will in the end develop liver metastases. Next to that, primary liver cancer, is a frequent cancer with fatal liver failure in the majority of patients. Selective internal radiation therapy (SIRT), has gradually been introduced over the recent years and is a promising, innovative albeit palliative treatment modality. The specific clinical background with regard to the indication and methodology of SIRT is presented and discussed in this paper.

[Combining CT and scintigraphy: SPECT-CT and PET-CT]. / CT combineren met scintigrafie: SPECT-CT en PET-CT.

In recent years tomographic hybrid scanners have been quickly introduced in nuclear medicine: single-photon emission computed tomography (SPECT)-CT and positron emission tomography (PET)-CT.- Both SPECT-CT and PET-CT techniques provide a higher diagnostic accuracy than conventional (non-tomographic, non-hybrid) bone scintigraphy (bone scan).- Differences between 99mTc hydroxymethylene diphosphonate (HDP) SPECT-CT or 99mTc methylene diphosphonate (MDP) SPECT-CT and 18F-fluoride PET-CT bone scanning relate to image quality, technique, availability, quantification possibilities, radiation dosimetry and financial cost.- Indications for these techniques will especially lie in the field of more accurate detection of skeletal metastases than with bone scans, patients with unexplained musculoskeletal pain, the diagnostic stage after conventional X-ray and/or MRI, and quantification of bone metabolism.

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

AIM: The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. METHODS: Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. RESULTS: Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. CONCLUSION: The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging.

BACKGROUND: Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity. PATIENTS AND METHODS: Chemonaive patients with stage IIIb or IV non-squamous NSCLC were treated with bevacizumab 15 mg/kg every 3 weeks and erlotinib 150 mg daily until progression. Primary end point was non-progression rate (NPR) at 6 weeks. Tumor response was measured with computed tomography, 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). KRAS and EGFR mutations were assessed in tumor samples. RESULTS: Forty-seven patients were included. Median follow-up was 15.2 months. NPR at 6 weeks was 75%. Median progression-free survival (PFS) was 3.8 [95% confidence interval (CI) 2.3-5.4] months and median overall survival (OS) was 6.9 (95% CI 5.5-8.4) months. Toxicity was mainly mild. The presence of KRAS (n = 10) or EGFR mutations (n = 5) did not influence outcome. After 3 weeks of treatment, >20% decrease in standard uptake value as measured with positron emission tomography predicted for longer PFS (9.7 versus 2.8 months; P = 0.01) and >40% decrease in K(trans) as assessed by DCE-MRI did not predict for longer PFS. CONCLUSIONS: First-line treatment with bevacizumab and erlotinib in stage IIIb/IV NSCLC resulted in an NPR of 75%. OS was however disappointing. Early response evaluation with FDG-PET is the best predictive test for PFS.

The role of (124)I-PET in diagnosis and treatment of thyroid carcinoma.

Iodine-124 is a positron-emitting iodine isotope, enabling measurement of iodine uptake using positron emission tomography (PET). There is a number of situations where the use of (124)I-PET/computed tomography (CT) can improve the current clinical practice in the diagnosis and treatment of thyroid cancer. Firstly, (124)I-PET/CT can aid in the staging of patients, because of better detection of metastatic disease and measurement of metabolic tumour volume, and thus separate low-risk from high risk patients. Secondly, the much higher sensitivity and spatial resolution of PET compared to gamma scintigraphy can also improve detection of recurrent disease. Furthermore, (124)I-PET can be used for patient-specific radioiodine therapy radiation dosimetry. Simultaneous administration of the therapeutic dose of (131)I and a tracer dose of (124)I allows for accurate measurement of iodine uptake during therapy. The decay scheme of (124)I, with few positrons and many gamma rays emitted per decay, often simultaneously, poses a challenge to quantitative PET imaging. Improved correction methods and the use of last-generation PET/CT scanners with faster electronics and better energy resolution can overcome this.

Targeted therapy in nuclear medicine--current status and future prospects.

In recent years, a number of new developments in targeted therapies using radiolabeled compounds have emerged. New developments and insights in radioiodine treatment of thyroid cancer, treatment of lymphoma and solid tumors with radiolabeled monoclonal antibodies (mAbs), the developments in the application of radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine and peptides and the position of locoregional treatment in malignant involvement of the liver are reviewed. The introduction of recombinant human thyroid-stimulating hormone and the possibility to enhance iodine uptake with retinoids has changed the radioiodine treatment protocol of patients with thyroid cancer. Introduction of radiolabeled mAbs has provided additional treatment options in patients with malignant lymphoma, while a similar approach proves to be cumbersome in patients with solid tumors. With radiolabeled small molecules that target specific receptors on tumor cells, high radiation doses can be directed to tumors in patients with disseminated disease. Radiolabeled somatostatin derivatives for the treatment of neuroendocrine tumors are the role model for this approach. Locoregional treatment with radiopharmaceuticals of patients with hepatocellular carcinoma or metastases to the liver may be used in inoperable cases, but may also be of benefit in a neo-adjuvant or adjuvant setting. Significant developments in the application of targeted radionuclide therapy have taken place. New treatment modalities have been introduced in the clinic. The concept of combining therapeutic radiopharmaceuticals with other treatment modalities is more extensively explored.

Clinical radionuclide therapy dosimetry: the quest for the "Holy Gray".

INTRODUCTION: Radionuclide therapy has distinct similarities to, but also profound differences from external radiotherapy. REVIEW: This review discusses techniques and results of previously developed dosimetry methods in thyroid carcinoma, neuro-endocrine tumours, solid tumours and lymphoma. In each case, emphasis is placed on the level of evidence and practical applicability. Although dosimetry has been of enormous value in the preclinical phase of radiopharmaceutical development, its clinical use to optimise administered activity on an individual patient basis has been less evident. In phase I and II trials, dosimetry may be considered an inherent part of therapy to establish the maximum tolerated dose and dose-response relationship. To prove that dosimetry-based radionuclide therapy is of additional benefit over fixed dosing or dosing per kilogram body weight, prospective randomised phase III trials with appropriate end points have to be undertaken. Data in the literature which underscore the potential of dosimetry to avoid under- and overdosing and to standardise radionuclide therapy methods internationally are very scarce. DEVELOPMENTS: In each section, particular developments and insights into these therapies are related to opportunities for dosimetry. The recent developments in PET and PET/CT imaging, including micro-devices for animal research, and molecular medicine provide major challenges for innovative therapy and dosimetry techniques. Furthermore, the increasing scientific interest in the radiobiological features specific to radionuclide therapy will advance our ability to administer this treatment modality optimally.

A case of abdominal mesothelioma diagnosed by indium-III leucocyte scintigraphy.

We present a case of peritoneal mesothelioma that presented with fever of unknown origin and an elevation in the inflammatory parameters. Radiological imaging did not reveal a diagnosis. Because of tumour-associated inflammatory activity, indium-III leucocyte scintigraphy enabled us to establish a diagnosis. To our knowledge, the use of indium-III leucocyte scintigraphy in peritoneal mesothelioma has not been reported previously.

Depression and anxiety during isolation and radionuclide therapy.

The combination of a diagnosis of malignancy and hospitalization, isolation and radioactivity of a radionuclide therapy may have an important effect on the psychological equilibrium of patients and may hamper compliance and acceptability. We performed a psychiatric evaluation in order to study psycho-pathological manifestations and underlying personality related vulnerabilities. During radioisolation, 48 patients (24 male, 24 female; mean age 57.8 years) with a malignant (n=26) or non-malignant (n=22) pathology who needed isolation for radionuclide therapy, completed a series of questionnaires in order to assess anxiety (Spielberger State and Trait Anxiety Inventory; STAI), depression (Beck Depression Inventory; BDI), hopelessness (Beck Hopelessness Scale; BHS), personality characteristics (Temperament and Character Inventory; TCI) and coping strategies (Utrecht's Coping List; UCL). Compared to patients with low state anxiety, patients who experienced a high level of state anxiety showed higher levels of depression (t=-2.10; P=0.04) and hopelessness (t=-4.20; P=<0.001). Their personality was characterized by significantly higher scores on harm avoidance (t=-2.78; P=0.008) and lower scores on self-directedness (t=3.12; P=0.003). Coping strategies were more passive (t=-2.43; P=0.02), avoiding (t=-2.15; P=0.04) and less well aimed (t=2.64; P=0.01). Surprisingly, the nature of disease (malignant versus non-malignant) did not influence these results, nor was there a difference between males and females, age, years of education, having a relationship or not, or the duration of hospitalization. Thus, contrary to what may be expected in isolation with radionuclide therapy, subgroups such as women, elderly, cancer patients or lower educated people do not, a priori, exhibit a higher state anxiety level. Our study shows these levels to be closely related to individual personality traits and coping strategies that are inadequate for the situation. Screening for trait anxiety before admission can be easily done and may guide interventions aimed at increasing patient comfort and acceptability.

Intra-arterial radionuclide therapy for liver tumours: effect of selectivity of catheterization and 131I-Lipiodol delivery on tumour uptake and response.

Several authors have demonstrated the good tolerance of hepatic intra-arterial 131I-Lipiodol therapy and report survival rates of 21-25% after 1 year in inoperable patients. This study explored the possibility that more selective hepatic arterial instillation could be a strategy for increasing tumoural uptake and response of 131I-Lipiodol. Between June 1999 and September 2001 we selected 24 patients: 14 received a selective instillation of 131I-Lipiodol to the proper hepatic artery (SEL group); and 10 received a hyperselective instillation in the right or left hepatic artery (HYP-SEL group). The individual 131I-Lipiodol activity as a per cent of the injected activity per millilitre of tumour (%IA/ml tumour) was correlated with the selectivity of instillation in 28 tumours and with tumour response in 24 tumours. Differences in tumour response or tumour uptake between the SEL and HYP-SEL groups were not significant. In general, we observed a %IA/ml tumour of 0.05-2.6% for the uptake of 131I-Lipiodol. The uptake was significantly higher in responsive disease than in stable or progressive disease (P=0.002). A large tumour volume was invariably related to low uptake of 131I-Lipiodol and progressive disease (P=0.008). In conclusion, our study does not support the general use of hyper-selective or super-selective intra-arterial administration of 131I-Lipiodol. This result may be extrapolated to similar types of intra-arterial, loco-regional hepatic radionuclide therapy.

Thyroid uptake and radiation dose after (131)I-lipiodol treatment: is thyroid blocking by potassium iodide necessary?

In radionuclide therapy with iodine-131 labelled pharmaceuticals, free (131)I may be released and trapped by the thyroid, causing an undesirable radiation burden. To prevent this, stable iodide such as potassium iodide (KI) can be given to saturate the thyroid before (131)I is administered. The guidelines of the European Association of Nuclear Medicine do not, however, recommend special precautions when administering (131)I-lipiodol therapy for hepatocellular carcinoma. Nevertheless, some authors have reported (131)I uptake in the thyroid as a consequence of such therapy. In this study, the influence of prophylactic KI on the thyroid uptake and dose (MIRD dosimetry) was prospectively investigated. (131)I-lipiodol was given as a slow bolus selectively in the proper hepatic artery or hyperselectively in the right and/or left hepatic artery. Patients were prospectively randomised into two groups. One group received KI in a dose of 100 mg per day starting 2 days before (131)I-lipiodol administration and continuing until 2 weeks after therapy (KI group; n=31), while the other group received no KI (non-KI group; n=37). Thyroid uptake was measured scintigraphically as a percentage of administered activity 7 days after (131)I-lipiodol ( n=68 treatments). The absorbed radiation dose to the thyroid was assessed by scintigraphy after 7 and 14 days using a mono-exponential fitting model and MIRD dosimetry ( n=40 treatments). The mean activity of (131)I-lipiodol administered was 1,835 MBq in a volume of 2 ( n=17) or 4 ( n=51) ml. Thyroid uptake was lower in the KI group, being 0.23%+/-0.06% of injected activity ( n=31) compared with 0.42%+/-0.20% in the non-KI group ( n=37); the mean thyroid dose was 5.5+/-1.6 Gy in the KI group ( n=19) versus 11.9+/-5.9 Gy in the non-KI group ( n=21). These differences were statistically significant ( P<0.001). No effect of the amount of added cold lipiodol (4 vs 2 ml total volume) or selectivity of (131)I-lipiodol administration was evident ( P>0.1). (131)I-lipiodol is associated with a generally low thyroid uptake and dose that may be significantly decreased by KI premedication. Given the low cost and the very good tolerance of the KI treatment, we believe the use of KI should be recommended in the majority of the patients.

Quality of life assessment in radionuclide therapy: a feasibility study of the EORTC QLQ-C30 questionnaire in palliative (131)I-lipiodol therapy.

The good tolerance of radionuclide therapy has frequently been proposed as a major advantage. This study explored the feasibility of using the EORTC QLQ-C30 questionnaire in palliative iodine-131 lipiodol therapy for hepatocellular carcinoma. Questionnaires were completed during interviews in which all symptoms, co-morbidity and medication were assessed at baseline within 1 week before (131)I-lipiodol therapy, and subsequently after 1 and 3 months, in 20 patients treated with locoregional, intra-arterial (131)I-lipiodol therapy with or without cisplatin. Principal observations were that (1) a number of important scales, i.e. overall quality of life, physical functioning and pain, worsened between 0 and 3 months after (131)I-lipiodol therapy, irrespective of tumour response, and (2) the occurrence of clinical side-effects was associated with a negative impact on quality of life and physical functioning 1 and 3 months after (131)I-lipiodol. The QLQ-C30 can be regarded as a feasible method for quality of life assessment in (131)I-lipiodol therapy for hepatocellular carcinoma and possibly in other radionuclide therapies. These observations should be related to the impact of other treatment modalities on quality of life.

SPECT neuropsychological activation procedure with the Verbal Fluency Test in attempted suicide patients.

Performance on the Verbal Fluency Test, as a measure of the ability of initiating processes, is reduced in depressed suicidal patients. The hampered results in this prefrontal executive task parallel the reduction in prefrontal blood perfusion and metabolism in depressed subjects. A neuropsychological activation study with the verbal fluency paradigm could evaluate a possible blunted increase in perfusion in the prefrontal cortex in depressed suicidal patients. Twenty clinically depressed patients who had recently attempted suicide and 20 healthy volunteers were included in a single photon emission computed tomography (SPECT) split-dose activation study following a verbal fluency paradigm. Statistical parametric mapping was used to determine voxelwise significant changes. Differences in regional cortical activation between the letter fluency and category fluency tasks in attempted suicide patients were found. These patients showed a blunted increase in perfusion in the prefrontal cortex. Methodological restrictions concerning group uniformity, medication bias and subjective effort of the participants are discussed. Our findings indicate a blunted increase in prefrontal blood perfusion as a possible biological reason for reduced drive and loss of initiative in attempted suicide patients.

Combining iodine-131 Lipiodol therapy with low-dose cisplatin as a radiosensitiser: preliminary results in hepatocellular carcinoma.

A prospective pilot trial was performed in 20 patients randomised to receive either (131)I-Lipiodol therapy alone (n=10) or (131)I-Lipiodol combined with a short low-dose cisplatin infusion (n=10), the aim being to evaluate the possible positive influence of a radiosensitiser on toxicity and tumour response. An activity of 1,354-2,128 MBq (mean 1,824 MBq) [36.6-57.5 mCi (mean 49.3 mCi)] (131)I-labelled Lipiodol was administered by selective instillation in the hepatic artery. Cisplatin was given in a dose of 30 mg/m(2) at day -1 and day +6 (day 0: (131)I-Lipiodol). The primary endpoint of this trial was toxicity of therapy; points of secondary interest were tumour response and survival at 6 months. With the use of cisplatin we found a higher percentage of stable or diminished tumour size (90%, vs 40% without). A benefit in group survival at 6 months was not evident. Low-grade stomatitis in one patient and minor changes in peripheral blood count were probably directly related to cisplatin, but its administration is unlikely to be associated with an excess of serious side-effects. The use of low-dose cisplatin infusion as a radiosensitising agent in (131)I-Lipiodol therapy for hepatocellular carcinoma seems safe and may be beneficial for tumour control. Larger patient groups are necessary for confirmation and to establish the future role of (131)I-Lipiodol in hepatocellular carcinoma.

The anti-tumoral activity of neoadjuvant intra-arterial 131I-lipiodol treatment for hepatocellular carcinoma: a pilot study.

BACKGROUND: The high recurrence rate after curative resection has stimulated the development of adjuvant treatment modalities, such as local embolization. This study was set up to investigate the anti-tumoral potential of neo-adjuvant 131I-lipiodol administration before liver transplantation. METHODS: In this preliminary, prospective study we treated 10 consecutive HCC patients by intra-arterial injection of 131I-lipiodol into the hepatic artery followed by liver transplantation within 1-9 months (mean 3.4). After hepatic catheterization, 1332-2146 MBq (mean 1887 MBq) or 36-58 mCi (mean 51 mCi) was instilled as selective as possible, depending on the distribution of the tumors: non-selectively in the hepatic artery propria (n = 4), selectively in the right and/or left hepatic artery (n = 3) or super-selectively in segmental arteries (n = 3). RESULTS: Anti-tumoral activity was regarded as obvious with 1) a strong decrease of alfa-fetoprotein (AFP), comparing the highest recorded value before and after 131I-lipiodol and/or 2) a downstaging in TNM classification on the posttherapy MRI as compared to the pre-therapy MRI and/or 3) tumors with > 50% necrosis on histo-pathology of the explanted liver, without previous chemoembolization. Either of these criteria were met by 5/10 (50%) of patients. A 4) downstaging in pTNM classification on histopathology compared to the TNM classification of the MRI and/or a 5) tumor necrosis of only 10-50% were regarded as possibly tumor-related but were not accepted as a single criteria of anti-tumoral activity. This was seen in 3/10 (30%) of patients. Clinical side-effects of the 131I-lipiodol therapy were generally mild with a temperature rise in two cases, nausea without vomiting in another two and upper back pain in one patient. In one patient progressive liver failure developed one week after 131I-lipiodol therapy necessitating premature liver transplantation after 4 weeks. CONCLUSION: With the use of stringent anti-tumoral criteria, this study shows evidence of an anti-tumoral effect in 50% of patients. Our data support the evaluation on larger patient numbers to confirm the promising anti-tumoral activity of 131I-lipiodol in HCC patients candidated for liver transplantation.

Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours.

AIM: The aim of the study was to determine the equivalent total body dose (ETBD) using the cytokinesis-blocked micronucleus assay in 22 131 I-meta-iodobenzylguanidine (131 I-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD 1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are correlated with the total body radiation dose according to the Medical Internal Radiation Dosimetry (MIRD) formalism. METHODS: For each patient, blood samples were taken immediately before and 1 week after 131I-MIBG therapy. The first blood sample was irradiated in vitro with 60Co gamma-rays to determine the dose-response curve. Micronuclei were scored in 1000 binucleated cells. By using the dose-response curve the ETBD was derived from the increase in micronuclei after 131I-MIBG therapy (second blood sample). Based on three consecutive biplanar scans taken at 3, 6 and 9 days post-administration respectively, the total body dose following the MIRD formalism was calculated. RESULTS: The micronucleus assay was evaluable in only 14 out of 22 131I-MIBG therapies due to cell division inhibition caused by previous chemotherapy treatments and lymphocyte dilution due to blood transfusions given shortly after 131I-MIBG therapy. For these 14 therapies, the mean micronucleus yield after 131I-MIBG therapy was significantly increased (P < 0.01) with a mean of 92 (SD 77) for neuroblastoma patients and with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the present study is greater than previously observed after 131I therapy and 89Sr therapy but much lower than after external beam radiotherapy. For all patients treated with multiple therapies, the initial increase in micronucleus yield had at least partially recovered by the time of the next therapy. This might be explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD 0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid patients was calculated. A reasonable correlation (R = 0.87) between the ETBD and the MIRD dose was obtained. The slope value of 0.75 can be explained by the low dose rate effect. CONCLUSIONS: The observation in the present study of important inter-individual variability in the total body dose, with the possibility of high dose values, suggests the necessity of individual dosimetry when administering 131I-MIBG therapy, especially considering that generally more than one therapy is given to each patient.

Transfer of normal 99mTc-ECD brain SPET databases between different gamma cameras.

A stereotactic, normal perfusion database is imperative for optimal clinical brain single-photon emission tomography (SPET). However, interdepartmental use of normal data necessitates accurate transferability of these data sets. The aim of this study was to investigate transfer of three normal perfusion databases obtained in the same large population of healthy volunteers who underwent sequential scanning using multihead gamma cameras with different resolution. Eighty-nine healthy adults (46 females, 43 males; aged 20-81 years) were thoroughly screened by history, biochemistry, physical and full neurological examination, neuropsychological testing and magnetic resonance imaging. After injection of 925 MBq technetium-99m labelled ethyl cysteinate dimer (ECD) under standard conditions, 101 scans were acquired from all subjects (12 repeat studies) on a triple-head Toshiba GCA-9300A (measured average FWHM 8.1 mm). Ninety-one sequential scans were performed on a dual-head Elscint Helix camera (FWHM 9.6 mm) and 22 subjects also underwent imaging on a triple-head Prism 3000 (FWHM 9.6 mm). Images were transferred to the same processing platform and reconstructed by filtered back-projection with the same Butterworth filter (order 8, cut-off 0.9 cycles/cm) and uniform Sorensen attenuation correction (mu = 0.09). After automated rigid intrasubject registration, all subjects were automatically reoriented to a stereotactic template by a nine-parameter affine transformation. The databases were analysed using 35 predefined volumes of interest (VOIs) with normalisation on total VOI counts. For comparison, the high-resolution data were smoothed with a 3D Gaussian kernel to achieve more similar spatial resolution. Hoffman phantom measurements were conducted on all cameras. Partial volume effects after smoothing varied between -6.5% and 10%, depending on VOI size. Between-camera reproducibility was 2.5% and 2.7% for the Toshiba camera versus the Helix and the Prism database, respectively. The highest reduction in between-camera variability was achieved by resolution adjustment in combination with linear washout correction and a Hoffman phantom-based correction. In conclusion, transfer of normal perfusion data between multihead gamma cameras can be accurately achieved, thereby enabling widespread interdepartmental use, which is likely to have a positive impact on the diagnostic capabilities of clinical brain perfusion SPET.