Perioperative PET/CT lymphoscintigraphy and fluorescent real-time imaging for sentinel lymph node mapping in early staged colon cancer.

PURPOSE: Using current optical imaging techniques and gamma imaging modalities, perioperative sentinel lymph node (SLN) identification in colon cancer can be difficult when the SLN is located near the primary tumour or beneath a thick layer of (fat) tissue. Sentinel lymph node mapping using PET/CT lymphoscintigraphy combined with real-time visualization of the SLN using near-infrared imaging has shown promising results in several types of cancer and may facilitate the successful identification of the number and location of the SLN in early colon cancer. METHODS: Clinical feasibility of PET/CT lymphoscintigraphy using preoperative endoscopically injected [89Zr]Zr-Nanocoll and intraoperative injection of the near-infrared (NIR) tracer Indocyanine Green (ICG) was evaluated in ten early colon cancer patients. Three preoperative PET/CT scans and an additional ex vivo scan of the specimen were performed after submucosal injection of [89Zr]Zr-Nanocoll. All SLNs and other lymph nodes underwent extensive pathological examination for metastases. A histopathological proven lymph node visible at preoperative PET/CT and identified at PET/CT of the specimen was defined as SLN. RESULTS: A total of 27 SLNs were harvested in seven out of eight patients with successful injection of both tracers. In one patient no SLNs were assigned preoperatively. In two patients injection of [89Zr]Zr-Nanocoll failed due to incorrect needle positioning. Twenty-one (78%) SLNs were found intraoperatively using NIR-imaging. Eleven of the 27 (41%) SLNs were located near the primary tumour (< 2 cm). Those six SLNs not found intraoperatively with NIR-imaging were all located close to the tumour. In all seven patients at least one SLN could be assigned at preoperative imaging 24 h after tracer administration. One SLN contained metastases detected by immunohistochemistry. No metastases were found in the non-SLNs. CONCLUSIONS: This study shows the potential of preoperative PET/CT lymphoscintigraphy to inform the surgeon about the number and location of SLNs in patients with early colon cancer. The additional use of NIR-imaging allows for intraoperative identification of these SLNs which are invisible with conventional white light imaging. Further research is necessary to improve and simplify the technique. We recommend perioperative SLN identification using a preoperative lymphoscintigraphy scan just before surgery approximately 24 h after injection. Additionally a postoperative scan of the specimen combined with intraoperative real-time NIR-imaging should be performed.

Pharmaceutical preparation of oxygen-15 labelled molecular oxygen and carbon monoxide gasses in a hospital setting.

BACKGROUND: Clinical positron emission tomography (PET) requires safe and effective PET radiopharmaceuticals. Tracers used for measuring oxygen consumption and blood volume are [(15)O]O(2) and [(15)O]CO, respectively. In general, these oxygen-15 labelled tracers are produced using a cyclotron that accelerates deuterons onto a target filled with (14)N(2) containing a trace of oxygen. In recent years, cyclotrons have been developed that only are capable of accelerating protons. The purpose of this study was to validate and assess such a cyclotron for production and administration of oxygen-15 labelled gasses in an hospital setting. METHODS: An RDS111 cyclotron (Siemens-CTI, Knoxville, USA) was validated for bolus production of [(15)O]O(2) and [(15)O]CO gasses. In addition, equipment was developed to administer these tracers to patients. RESULTS: Both [(15)O]O(2) and [(15)O]CO gasses could be produced in sufficient amounts, whilst meeting European Pharmacopeia requirements. Although produced oxygen-15 gasses contained a minor level of (11)C contamination, in clinical studies it was possible to correct for this contamination by delayed blood counting. CONCLUSION: An 11 MeV proton cyclotron combined with an in-house developed gas delivery system allows for the production and administration of sufficient amounts of [(15)O]-gasses for routine clinical PET studies in an hospital setting.

Radioimmunoscintigraphy of head and neck cancer using 99mTc-labeled monoclonal antibody E48 F(ab')2.

The diagnostic value of 99mTc-labeled monoclonal antibody E48 F(ab')2 (750 MBq, 1 mg) was evaluated in 10 patients with a histologically proven squamous cell carcinoma of the head and neck and with clinical evidence of cervical lymph node involvement. Preoperative findings on lymph node status obtained by radioimmunoscintigraphy (RIS), computerized tomography, magnetic resonance imaging, and palpation were defined per side (left and/or right side of the neck) as well as per lymph node level (I through V) and compared with the histopathological outcome of the neck dissection specimen. In 10 patients, all 8 known tumors at the primary site were detected by RIS. Furthermore, RIS was correct in 13 of 13 tumor involved neck sides and in 17 of 20 tumor involved lymph node levels. False-negative observations comprised 3 levels containing tumor deposits smaller than 1 cm in diameter, 2 of which were not detected by any other diagnostic modality. Palpation, computerized tomography, and magnetic resonance imaging were correct in, respectively, 13, 15, and 15 of the 20 tumor involved levels. There were 2 false-positive observations with monoclonal antibody E48 and 3 with palpation. No false-positive detections occurred with computerized tomography or magnetic resonance imaging. In two of the patients, RIS provided clinically important information which was not provided by any other diagnostic method. In one patient, recurrence of laryngeal carcinoma was established at the primary site after previous radiotherapy. In another patient, bilateral instead of unilateral lymph node involvement became apparent. These preliminary data indicate that radioimmunoscintigraphy with monoclonal antibody E48 may be helpful in the diagnosis of metastatic and recurrent head and neck cancer.

Time course of functional recovery of stunned and hibernating segments after surgical revascularization.

BACKGROUND: Recovery of function is possible in patients with ischemic cardiomyopathy when left ventricular dysfunction is caused by stunning or hibernation. It is plausible that recovery of function after revascularization may take a longer time in hibernating myocardium compared with stunned myocardium. Accordingly, the time courses of functional recovery in hibernating and stunned myocardium were compared. METHODS AND RESULTS: Patients (n=26) with ischemic cardiomyopathy undergoing surgical revascularization were studied; regional perfusion (resting (201)Tl single-photon emission CT), glucose utilization ((18)F-2-deoxyglucose single-photon emission CT), and contractile function (2D echocardiography) were assessed before revascularization. Dysfunctional segments with normal perfusion/glucose utilization were considered to be stunned, and dysfunctional segments with reduced perfusion/preserved glucose utilization were considered to be hibernating. Contractile function was reevaluated 3 months (early) and 14 months (late) after revascularization. Of the 266 dysfunctional segments, 57 (22%) were stunned, 62 (23%) were hibernating, and 147 (55%) were scar tissue. In stunned myocardium, contractile function improved significantly at 3 months, without further improvement at 14 months; 61% of the stunned segments improved at 3 months, and 9% improved at 14 months. In hibernating myocardium, contractile function improved at 3 months, with a further improvement at 14 months; 31% of the hibernating segments improved at 3 months, and 61% showed (additional) recovery at 14 months. CONCLUSIONS: Stunned myocardium is likely to demonstrate early recovery of function, whereas hibernating myocardium may take a longer time to (fully) recover in function after revascularization.

Prediction of recovery of myocardial dysfunction after revascularization. Comparison of fluorine-18 fluorodeoxyglucose/thallium-201 SPECT, thallium-201 stress-reinjection SPECT and dobutamine echocardiography.

OBJECTIVES: We compared three techniques to predict functional recovery after revascularization. BACKGROUND: Recently, fluorine-18 (F-18) fluorodeoxyglucose in combination with single-photon emission computed tomography (SPECT) has been proposed to identify viable myocardium, Thallium-201 reinjection and low dose dobutamine echocardiography are used routinely for this purpose. METHODS: Seventeen patients (mean [+/- SD] left ventricular ejection fraction 36 +/- 11%) were studied. Regional and global ventricular function were evaluated before and 3 months after revascularization by echocardiography and radionuclide ventriculography, respectively. Myocardial F-18 fluorodeoxyglucose uptake (during hyperinsulinemic glucose clamping) was compared with rest perfusion assessed with early thallium-201 SPECT. On a separate day, low dose dobutamine echocardiography and post-stress thallium-201 reinjection SPECT were simultaneously performed. RESULTS: The sensitivities for F-18 fluorodeoxyglucose/thallium-201, thallium-201 reinjection and low dose dobutamine echocardiography to assess recovery were 89%, 93% and 85%, respectively; specificities were 77%, 43% and 63%, respectively. Stepwise logistic regression indicated that F-18 fluorodeoxyglucose/ thallium-201 was the best predictor. In hypokinetic segments, the combination of F-18 fluorodeoxyglucose/thallium-201 and low dose dobutamine echocardiography was the best predictor. Global function improved (left ventricular ejection fraction increased > 5%) in 6 patients and remained unchanged in 11. All three techniques correctly identified five of six patients with improvement. Fluorine-18 fluorodeoxyglucose/thallium-201 identified all patients without improvement; low dose dobutamine echocardiography identified 9 of 11 without improvement; and thallium-201 reinjection identified 6 of 11 patients without improvement. CONCLUSIONS: Fluorine-18 fluorodeoxyglucose/thallium-201 SPECT was superior to the other techniques in assessing functional recovery. Integration of metabolic and functional data is necessary, particularly in hypokinesia, for optimal prediction of improvement of regional function.

Prediction of improvement of contractile function in patients with ischemic ventricular dysfunction after revascularization by fluorine-18 fluorodeoxyglucose single-photon emission computed tomography.

OBJECTIVES: We evaluated the use of fluorine-18 fluorodeoxyglucose (FDG) and single-photon emission computed tomography (SPECT) to predict improvement of left ventricular ejection fraction (LVEF) after revascularization. BACKGROUND: FDG SPECT has recently been proposed for assessment of myocardial viability. However, FDG SPECT still awaits validation in terms of predicting improvement of contractile function after revascularization in patients with poor left ventricular (LV) function. METHODS: Fifty-five patients with contractile dysfunction (including 22 with LVEF < 30%) underwent FDG SPECT during hyperinsulinemic glucose clamping and early thallium-201 SPECT (to assess perfusion). Improvement of LV function was evaluated 3 months after revascularization with echocardiography and radionuclide ventriculography. RESULTS: The 55 patients were arbitrarily classified into two groups: 19 with three or more viable, dysfunctional segments on FDG SPECT and 36 with less than three viable, dysfunctional segments. LVEF increased significantly in the first group, from 28 +/- 8% (mean +/- SD) before to 35 +/- 9% (p < 0.01) after revascularization. In the second group, LVEF remained unchanged after revascularization (45 +/- 14% vs. 44 +/- 14%, p = NS). The 22 patients with severely depressed LV function were similarly classified into two groups: 14 with three or more viable segments on FDG SPECT in whom LVEF improved significantly (25 +/- 6% vs. 32 +/- 6%) and 8 with less than three viable segments in whom LVEF remained unchanged (24 +/- 6% vs. 25 +/- 6%). CONCLUSIONS: This study shows that FDG SPECT can identify patients in whom LV function improves after revascularization. Because SPECT is widely available, this technique may contribute to more routine use of FDG for determination of viability.

Biodistribution of radiolabeled monoclonal antibody E48 IgG and F(ab')2 in patients with head and neck cancer.

Biodistribution and pharmacokinetics of radiolabeled mAb E48 IgG and E48 F(ab')2 were analyzed and compared in 39 patients with histologically proven squamous cell carcinoma of the head and neck who were included in a radioimmunoscintigraphy study and underwent surgery 44 h after injection. Three groups of patients were distinguished: group 1 (n = 19) received technetium-99m (99mTc)-labeled E48 F(ab')2, group 2 (n = 9) received 99mTc-labeled E48 IgG, and group 3 (n = 11) received 99mTc- and 131I-labeled E48 IgG as well as 125I-labeled F(ab')2. Two patients in group 1 and four patients in group 3 received a high mAb dose (10-50 mg), while all other patients received a low mAb dose (1-4 mg). From all patients in groups 2 and 3 biopsies from the surgical specimen were obtained 44 h postinjection. Tumor uptake of 99mTc-labeled E48 IgG was high, ranging from 0.007 to 0.082% of the injected dose/g, with a mean of 0.031 +/- 0.020% of the injected dose/g. The mean tumor:nontumor ratio of this conjugate was 2.8 for mucosa, 4.6 for bone marrow aspirate, 4.1 for blood, 20.3 for fat, and 21.0 for muscle. Activity uptake in tumor positive lymph nodes was 4.7 times higher as compared to negative lymph nodes. Sixteen h postinjection radioimmunoscintigraphy revealed activity uptake in the primary tumor, lymph node metastases, oral cavity, and adrenal glands. Using regions of interest, the uptake in the adrenal glands was estimated to be 0.050% of the injected dose/g. If a high mAb dose was used, no adrenal glands were visualized and the uptake in the oral cavity was clearly diminished, while the tumor uptake and tumor:nontumor ratios were increased. The mean elimination half-lifes t1/2 alpha and t1/2 in plasma were: for E48 IgG (n = 20) 6.6 +/- 2.6 and 54.1 +/- 24.3 h and for E48 F(ab')2 (n = 19) 2.3 +/- 0.4 and 19.9 +/- 4.6 h, respectively. Tumor uptake of 131I-labeled E48 IgG was 49% higher than of 125I-labeled F(ab')2. For most tissues except normal oral mucosa, tumor:nontumor ratios were slightly higher for F(ab')2 than for IgG. The present study shows that mAb E48 accumulates selectively and to a high level in head and neck squamous cell carcinoma. Although no definite conclusions can be drawn as to which mAb form is more suitable, IgG or F(ab')2, mAb E48 seems to have potential for radioimmunotherapy in head and neck squamous cell carcinoma patients.

Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET).

PURPOSE: To determine the concordance of a prototype dual head coincidence camera (LSO-PS) and full ring PET (BGO-PET) using (18)F-fluorodeoxyglucose (FDG) in the evaluation of pulmonary nodules (PNs). MATERIALS AND METHODS: Patients referred for evaluation of < or =3 PNs (< or =3 cm diameter) were prospectively studied on the same day with both BGO-PET and LSO-PS. Imaging was performed at 60 and 120 min after injection of 370MBq FDG, respectively. Images were independently interpreted by four observers with each observer blinded to the other modality for the same patient. Lesions were scored in terms of relative intensity versus background. Non-attenuation corrected (nonAC) BGO-PET was used as the reference test. RESULTS: Forty-seven patients with 54 PNs (mean diameter 1.7 cm, S.D. 0.7) were included. Twelve nodules were in the < or =1.0 cm - 27 in the 1.1-2.0 cm - and 15 in the 2.1-3.0 cm range. Interobserver agreement was similar for both FDG imaging modalities. Using a sensitive assessment strategy with LSO-PS (> or = faint intensity deemed positive), there was a 97% (38/39, 95%CI 87-100%) concordance with BGO-PET and one false positive case with LSO-PS. Conservative reading (moderate or intense intensity deemed positive) resulted in a 92% (36/39, 95%CI 80-97%) concordance with BGO-PET, without false positives. The only lesion missed by LSO-PS using both assessment strategies involved a nodule 1.5 cm diameter that demonstrated moderate increased FDG uptake on BGO-PET. CONCLUSION: Depending on the test positivity criteria, LSO-PS demonstrates a high concordance (92-97%) with nonAC BGO-PET for the characterization of pulmonary nodules.

Determinants of bone mineral density and risk factors for osteoporosis in healthy elderly women.

Bone mineral density (BMD) and risk factors for osteoporosis were assessed in 348 apparently healthy women over 70 years of age (mean 82.3 years). BMD was measured at both hips and the dominant distal radius. With stepwise multiple regression the best determinants of BMD, selected from anthropometric measurements, age, and years since menopause, were body weight and years since menopause (R2 between 0.07 and 0.20, p < 0.001). Risk and protective factors for osteoporosis were analyzed as indicator variables by multiple regression and corrected for confounding by age, years since menopause, and body weight. Significantly lower BMD at the hip was found in participants with impaired mobility (-5%) and users of loop diuretics (-5%). Use of thiazide(like) diuretics did not influence BMD significantly at any site. Users of oral corticosteroids had a significantly lower BMD at the hip and the distal radius (range -9.1 to -24.3%). Participants with a history of Colles' fracture (n = 56) had a significantly lower BMD at the other radius (-12.9%). The mean calcium intake from dairy products was high (mean 921 mg/day), only 11% having an intake below 500 mg. A relation of calcium intake with BMD could not be detected at any measurement site. We conclude that BMD cannot be adequately predicted in elderly women. Risk factors for low BMD in the elderly are low body weight, high number of years since menopause, impaired mobility, and use of loop diuretics and oral corticosteroids. Calcium intake was not a risk factor in this study, but the number of individuals on a low calcium intake was small.

Dual-energy X-ray absorptiometry for histologic bone sections.

In fundamental osteoporosis research precise and accurate assessment of the mineral quantity in histological bone sections is of particular importance when studying the local effects of implants releasing bone modulating agents. A potentially useful technique to estimate the bone mineral density (BMD) is dual-energy X-ray absorptiometry (DXA). A highly collimated (0.13 mm) Hologic 2000 with a line spacing and point resolution of 0.13 mm was used. The mineral content was measured in regions of 3.1 mm(2). A ceramic hydroxyapatite (CHA) phantom was developed as a reference standard. The phantom was made of a single-phase hydroxyapatite starting powder by compressing and sintering at 1000 degrees Celsius. The true density was 3.14 + or - 0.001 g/cm(3). The calcium/phosphorus ratio was close to the theoretical one of 1.67. The mean precision error expressed as the coefficient of variation (CV) of the mineral density (MD) measurements of the phantoms with thicknesses of 1, 2, and 3 mm was 0.2%. Embedded undecalcified alveolar bone sections of dogs (0.0015-1 mm in thickness) were scanned simultaneously with a phantom 1 mm in thickness. The precision error (CV) of the BMD measurements calculated by DXA for sections > or = 0.1 mm and with a BMD > or = 0.14 g/cm(2) was 0.81%. There was a linear relationship between the BMD calculated by DXA and the estimated BMD in the histological bone sections by means of the true density of the phantom. It is concluded that DXA using a standard CHA phantom is a precise and accurate method to measure MD changes as small as 1% in histological bone areas of 3.1 mm(2) provided that the loss or gain in BMD is > or = 0.14 g/cm(2).

Consequences of childhood-onset growth hormone deficiency for adult bone mass.

To assess the implications of prolonged growth hormone deficiency (GHD) for the acquisition and maintenance of bone mass, bone mineral density (BMD) was measured in 70 adult males (mean age 26.7 +/- 4.5 years) with childhood-onset GHD, 7.4 +/- 4.2 years after discontinuation of previous GH therapy. Because most of these patients were short (mean height 165.8 +/- 6.6 cm), the influence of body height on standard BMD measurements, conventionally reported as the areal density (BMDarea, expressed in g/cm2), was analyzed in a group of age-matched healthy males. In GHD patients, BMDarea was significantly reduced at the lumbar spine (Z score -1.59 +/- 1.08, p < 0.001) as well as at the nondominant hip (Z score -1.18 +/- 0.95, p < 0.001). The reduction in BMDarea was similar for patients with isolated GHD (N = 25) and those with combined deficiencies of GH and luteinizing hormone (N = 40). In patients and controls, BMDarea was positively correlated with body height, a relation that was attributed to skeletal size. Bone dimensions were significantly smaller in patients than in controls, and therefore it was hypothesized that the difference in areal density between patients and controls might be confounded by differences in bone size. Measured bone mineral content corrected for the estimated bone volume (BMDvolume, expressed in g/cm3) remained significantly reduced (Z score: lumbar spine, -0.90 +/- 1.08, p < 0.001; femoral neck, -0.74 +/- 1.00, p < 0.001), but the differences between GHD patients and controls were less than indicated by BMDarea (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound measurements in the calcaneus: precision and its relation with bone mineral density of the heel, hip, and lumbar spine.

Broadband ultrasound attenuation (BUA) and speed of sound (SOS) in the heel are suggested to measure bone density and structure and to predict fracture risk. Short-term precision (five consecutive measurements in 1 h) and long-term precision (six within 3 months) of ultrasound parameters were studied in 20 healthy subjects. The coefficient of variation (CV) did not change over a 3-month period for SOS (1.3%). Short-term precision of BUA was 3.4% (CV) and long-term precision was 4.9% (CV) (not significantly different: p = 0.09). Relationships between ultrasound parameters and BMD at various sites were examined in 42 subjects. BMD at the heel was assessed at the location corresponding to that of the ultrasound measurements (BMDheel). Correlation coefficients, corrected for imprecision in the measurements, for BUA and SOS vs. BMDheel, were 0.81 and 0.76, respectively. The correlation coefficients between heel measurements (BUA, SOS, and BMDheel) and BMD in the hip and lumbar spine ranged from 0.37 to 0.57. The relationships between BUA, SOS, and BMDheel vs. BMD of the hip were modified by physical activity and body weight. Higher physical activity and body weight were associated with higher BMD values at the hip. BUA values < 60 dB/MHz predicted BMD at the femoral neck < 0.70 g/cm2 with a sensitivity and specificity of 80% and 93%, respectively. After the age of 30, 11 participants had sustained vertebral fractures and 12 participants nonvertebral osteoporotic fractures. BUA and SOS values were significantly lower in fracture patients than in participants without fractures. It can be concluded that ultrasound measurements at the heel correlate well to BMD at the same site. BUA can predict BMD at the hip and is lower when the subject has sustained fractures.

Additional weight-bearing during exercise is more important than duration of exercise for anabolic stimulus of bone: a study of running exercise in female rats.

Mechanical loading is necessary for maintenance of skeletal integrity, but the most effective type, intensity, and duration of exercise are not known. In vivo experiments have indicated that the strain generated by the stimulus is more important than the duration of the stimulus. To elucidate this question, we studied 5-month-old female Wistar rats exercised on a motor-driven exercise belt for 17 weeks, 5 days per week (average velocity 20 m/min). Group 1 served as controls, group 2 was trained for 30 min, group 3 was trained for 30 min with a 50-g backpack, and group 4 was trained for 15 min with a 50-g backpack. Total body bone mineral content (BMC), bone mass of the lower extremities (LEBMC), total body lean soft-tissue mass (LSTM), and total body fat-tissue mass (FTM) were measured by dual-energy absorptiometry (DXA) at 0, 6, and 17 weeks. The BMC increased more in group 4 than in controls (15% vs. 8%, p < 0.03). In the other two intervention groups, no significant increases of total body BMC occurred compared with controls, although a trend was observed (12%). The LEBMC increased significantly in all exercising groups after 17 weeks, being 16% in group 2, 15% in group 3, and 20% in group 4, compared with 6% in controls (p < 0.05). The increase in LSTM after 6 weeks was most pronounced in group 3, at 20%, compared with 10% in the control group (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Tumour localisation with 131I-labelled human IgM monoclonal antibody 16.88 in advanced colorectal cancer patients.

Human IgM monoclonal antibody 16.88 recognised an intracellular antigen strongly expressed in colorectal cancer tissue in 51% of our patients. Tumour localisation was carried out with 185 MBq 131I-16.88 (8 mg) in 20 of these patients with advanced disease. In 16 patients (80%) immunoscintigraphy was positive in at least one organ site with disease. Of all sites, 55% could be visualized. In general, lesions less than 3 cm could not be detected. Sequential immunoscintigrams of liver metastases showed variable patterns. Initial "cold" lesions corresponded to liver metastases with poor blood supply as indicated by 99mTc-sulphur-colloid and 99mTc-HMPAO scintigraphy, respectively. The mean (S.D.) biological half-life (whole body clearance of radioactivity) was 37.6 (5.0) h. A second infusion of 131I-16.88 with the addition of high doses of unlabelled 16.88 could be done safely, but did not result in better visualisation of tumour lesions or affect radioactivity clearance from the body.

A dosimetric model for intrathecal treatment with 131I and 67Ga.

PURPOSE: Calculations were performed of absorbed dose distributions of the beta-emitter 131I and the Auger emitter 67Ga for intrathecal administration. METHODS AND MATERIALS: The proposed dosimetric model accounts for the macroscopic distribution of the activity, by means of a Medical Internal Radiation Dose Committee approach, and for the microscopic distribution of activity, by means of a point kernel technique. This point kernel approach was used in combination with a distance histogram technique, to study in more detail the absorbed dose distribution in the cerebro-spinal fluid, in the surface of the central nervous system, and in tumor sites. We simulated decreased uptake, as well as highly selective uptake in free-floating tumor cells and in meningeal lesions (1-16 cells thick). RESULTS: In case of limited access to lesions adherent to the pia mater, the beta-emitter 131I provides crossfire from the CSF, resulting in a higher absorbed dose (Gy/MBq) in these lesions as compared with the Auger emitter 67Ga. In case of increasing radionuclide uptake, the increment of the absorbed dose in the adherent lesions and the free floating cells from 67Ga is considerable because of the local deposition of energy by this radionuclide. CONCLUSIONS: The model might be useful to select the optimal emission characteristics of radionuclides applicable for intrathecal therapy, which is demonstrated in a comparison of the Auger emitter 67Ga and the beta-emitter 131I.

Absorbed dose distribution of the auger emitters 67GA and 125I and the beta-emitters 67CU, 90Y, 131I, and 186RE as a function of tumor size, uptake, and intracellular distribution.

PURPOSE: The influence of tumor volume, uptake of radioactive compounds in cells of tumors and normal tissues, and characteristics of the emitted ionizing particles on the efficacy of systemic radiation were studied. METHODS AND MATERIALS: The influence of these variables was assessed using a point kernel approach combined with a distance histogram technique. Simulation calculations were performed to assess dose distributions for three tumor sizes (phi = 200 microns, 2 mm, or 2 cm) and six radionuclides: 67Ga, 125I, 67Cu, 90Y, 131I, and 186Re. RESULTS: The energy deposition patterns depended on the relation of the tumor size and range of the emitted particles. Selective uptake was especially important in cases where the range was short compared to the dimension of the tumor. CONCLUSION: To attain a high dose for treatment of micrometastases, the use of Auger and conversion electron emitters (67Ga and 125I) or beta-emitters with emission spectra including low energetic electrons (67Cu and 131I) was recommended. The results demonstrated the complementary nature of selectivity of energy deposition and crossfire. This implied that for tumor cells or areas with reduced uptake, crossfire from radioactivity in surrounding cells or areas with selective uptake would be provided by intermediate (conversion electrons) or long-range (beta-particles) emissions.

Experimental and clinical evaluation of iterative reconstruction (OSEM) in dynamic PET: quantitative characteristics and effects on kinetic modeling.

UNLABELLED: The purpose of this study was to investigate the quantitative properties and effects of ordered-subset expectation maximization (OSEM) on kinetic modeling compared with filtered backprojection (FBP) in dynamic PET studies. Both phantom and patient studies were performed. METHODS: For phantom studies dynamic two-dimensional emission scans with 10-min frames and 20-min scan intervals were acquired over a 14-h period using an HR+ PET scanner. Various phantoms were scanned: 2-, 5-, 10-, and 20-cm-diameter phantoms filled with an 18F solution (300 kBq/mL) and a NEMA phantom filled with an 18F background (40 kBq/mL) and a cold or 11C insert (450 kBq/mL). Transmission (Tx) scans of 5-60 min were acquired. Data were reconstructed using FBP Hanning 0.5 and OSEM with 2-12 iterations and 12 or 24 subsets. Quantitative accuracy and noise characteristics were assessed. For patient studies, five cardiac, three oncologic, and three brain dynamic 18F-FDG scans were used. Five reconstructions were performed: FBP Hanning 0.5, and OSEM 2 x 12 and OSEM 4 x 16 with and without 5-mm full width at half maximum smoothing. Time-activity curves were calculated using volumes of interest. The input function was derived from arterial sampling. Metabolic rate of glucose (MRglu) was calculated with a standard two-tissue compartment model and Patlak analysis. RESULTS: Contribution of Tx noise to the reconstructed image was smaller for OSEM than for FBP. Differences in signal-to-noise ratio between FBP and OSEM depended on number of iterations and phantom size. Bias with OSEM was observed for regions enclosed within a 5- to 10-fold hotter background. For cardiac studies OSEM 2 x 12 and OSEM 4 x 16 resulted in 13% and 21% higher pixel values and 9% and 15% higher MRglu values compared with FBP. Smoothing decreased all these values to 2%. Similar results were found for most tumor studies. For brain studies MRglu of FBP and OSEM 4 x 16 agreed within 2%. Use of OSEM image-derived input functions for cardiac PET studies resulted in a decrease in calculated MRglu of about 15%. CONCLUSION: For most PET studies OSEM has equal quantitative accuracy as FBP. The higher pixel and MRglu values are explained by the better resolution of OSEM. However, OSEM does not provide accurate image-derived input functions for FDG cardiac PET studies because of bias in regions located within a hotter background.

Early treatment response in malignant lymphoma, as determined by planar fluorine-18-fluorodeoxyglucose scintigraphy.

Clinical oncology needs flexible techniques for routine monitoring of treatment response. We therefore compared planar 18F-fluorodeoxyglucose (FDG) with a conventional gamma-camera and a special collimator to 67Ga scintigraphy in 26 patients with malignant lymphoma during chemotherapy. The scintigraphic appearance of involved sites was essentially the same with both tracers: in patients eventually achieving complete remission, tracer distribution had normalized after two courses; high uptake reflected treatment failure; faint uptake was associated with variable outcome. For (re)staging, 67Ga may be preferable (higher contrast). To document the initial response, we performed FDG scintigraphy during the first course (n = 11). Effective treatment sharply reduced metabolic tumor activity within days and prior to volume response, whereas abnormal uptake persisted in treatment failure. Planar FDG scintigraphy may be a tool to assess the potentially prognostic initial response rate, preventing over-treatment and allowing a timely switch to more aggressive therapy.

Increased uptake of iodine-123-BMIPP in chronic ischemic heart disease: comparison with fluorine-18-FDG SPECT.

UNLABELLED: To evaluate the potential role of 15-p-[123I]iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP) for the assessment of myocardial viability, the patterns of BMIPP versus 18F-fluorodeoxyglucose (FDG) uptake were evaluated in patients with chronic ischemic heart disease. METHODS: Twenty-one patients with stable chronic coronary artery disease underwent resting TI SPECT to delineate myocardial perfusion followed by FDG SPECT to detect residual viability in regions showing perfusion defects. Resting BMIPP SPECT was obtained on a separate day. SPECT images were displayed as polar maps (13 segments) and analyzed semiquantitatively. A total of 273 segments were analyzed. RESULTS: In 87 (32%) of the segments, a perfusion defect was observed. In perfusion defects, the distributions of BMIPP/TI (mis)matches were significantly different (p < 0.0001) between the FDG viable (n = 42) and nonviable (n = 45) segments. A BMIPP/TI mismatch (BMIPP uptake higher than perfusion) was found in 74% of FDG viable segments, whereas a BMIPP/TI match (BMIPP uptake equal or lower than perfusion) was found in 69% of FDG nonviable segments. Agreement between matching or mismatching of segments was assessed to be 71%. Agreement was 81% when the data were analyzed on a patient basis. The observed frequency of BMIPP/TI mismatches was significantly higher (p < 0.05) in segments with an old myocardial infarction (20 of 36; 55%) than it was in subacute infarcted myocardium (5 of 21; 24%). CONCLUSION: In chronically hypoperfused myocardium, an increased BMIPP uptake relative to perfusion was detected, which is different from the decreased BMIPP uptake often reported in (sub)acute myocardial ischemia. Therefore, the interval from infarction may be an important factor in the interpretation of BMIPP scintigraphic data. Increased BMIPP uptake was associated with FDG/TI mismatches and may, therefore, confirm myocardial viability. Some segments with a FDG/TI mismatch, however, revealed a BMIPP/TI match. These segments may contain viable but more severely damaged tissue. Further studies on functional recovery are warranted to assess the significance of a BMIPP/perfusion (mis)match for tissue viability.