Noninvasive quantification of iodine-123-iomazenil SPECT

The feasibility of a noninvasive method for quantification of [123I]iomazenil binding using a standardized arterial input function and a single venous blood sample was assessed in normal volunteers. METHODS: Serial SPECT images and blood data from six healthy male volunteers after intravenous injection of [123I]iomazenil were used. The standardized input function was derived by averaging the six subjects' arterial curves. Individual input functions were estimated by calibrating the standardized input function with one-point venous blood radioactivity concentration. Ligand transport (K1) and receptor binding were computed from the estimated input functions and two separate SPECT scans using a table look-up procedure based on a three-compartment, two-parameter model. Reference values for K1 and receptor binding were determined from the serial SPECT data and individual arterial curves using a three-compartment, three-parameter model and curve fitting. RESULTS: Analyses of the error caused by the calibration in relation to the time postinjection revealed that the optimal calibration time was 30 min postinjection. Receptor binding obtained by this simplified method correlated well with the reference values (r = 0.941) and was estimated within an error of 10% in the cerebral cortical regions. Although the estimated K1 showed relatively poor correlation (r = 0.699) with the reference value, it was an excellent relative measure in each subject. CONCLUSION: Our method provided an absolute measure of the benzodiazepine receptor binding and a relative measure of ligand transport from two SPECT scans and a venous blood sample. This method would be useful for quantitative assessment of benzodiazepine receptors in clinical settings.     

Transient hypothyroidism after iodine-131 therapy for Grave's disease

We studied 355 patients with Grave's disease to characterize transient hypothyroidism and its prognostic value following 131I therapy. METHODS: The patients received therapeutic 131I treatment as follows: 333 received a dose < 10 mCi (6.6 +/- 1.9 mCi) and 22 received a dose > 10 mCi (12.8 +/- 2.9 mCi). Diagnosis of transient hypothyroidism was based on low T4, regardless of TSH within the first year after 131I followed by recovery of T4 and normal TSH. RESULTS: After administration of < 10 mCi 131I, 40 patients developed transient hypothyroidism during the first year; transient hypothyroidism was symptomatic in 15. There was no transient hypothyroidism after high doses (> 10 mCi) of 131I. Iodine-131 uptake > 70% at 2 hr before treatment was a risk factor for developing transient hypothyroidism (Odds ratio 2.8, 95% confidence interval 0.9-9.4). At diagnosis of transient hypothyroidism, basal TSH levels were high (51%), normal (35%) or low (14%); therefore, the transient hypothyroidism was not centralized. If hypothyroidism developed during the first 6 mo after basal TSH > 45 mU/liter ruled out transient hypothyroidism. CONCLUSION: The development of transient hypothyroidism and its hormonal pattern did not influence long-term thyroid function. Since no prognostic factors reliably predicted transient hypothyroidism before 131I or at the time of diagnosis, if hypothyroidism appears within the first months after 131I, the reevaluation of thyroid function later is warranted to avoid unnecessary chronic replacement therapy.     

Thymic uptake of iodine-131 in the anterior mediastinum

Two thyroidectomized patients with a history of differentiated thyroid carcinoma are presented who had nonmetastatic mediastinal 131I uptake following therapeutic doses of 131I. Chest CT scans in both patients demonstrated an anterior mediastinal mass. Surgical excision in one patient and a percutaneous CT-guided fine needle aspiration biopsy in the other disclosed normal thymus tissue. Iodine-131 uptake in the anterior mediastinum in patients thyroidectomized for follicular or papillary thyroid carcinoma may represent the thymus.     

Bivalent hapten-bearing peptides designed for iodine-131 pretargeted radioimmunotherapy

BACKGROUND: Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. AIMS: To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. PATIENTS: Consecutive patients with acute variceal haemorrhage. METHODS: Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 pg/h octreotide (n = 73), or emergency sclerotherapy (n = 77). RESULTS: Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p = 0.06). CONCLUSIONS: The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment.     

Nonmyeloablative iodine-131 anti-B1 radioimmunotherapy as outpatient therapy

The expected effective dose equivalent to an individual from contact with 131I anti-B1 radioimmunotherapy (RIT) patients released immediately after therapeutic infusion was estimated. METHODS: Effective dose equivalents were calculated retrospectively using data acquired on 46 patients treated with 1311 anti-B1 RIT as inpatients. Effective dose equivalents to members of the public were estimated using the method published in the Nuclear Regulatory Commission (NRC) Regulatory Guide 8.39, assuming the administered activity, the patient-specific effective half-life, the 0.25 occupancy factor, and no photon attenuation. Effective dose equivalents also were estimated using ionization chamber dose rates, measured immediately after therapeutic infusion and integrated to total decay based on the measured effective half-life. RESULTS: For the whole-body treatment absorbed dose limit of 75 cGy (75 rad), the administered 131I activity ranged from 2.1 to 6.5 GBq (56 to 175 mCi), and the measured dose rate at 1 m ranged from 70 to 190 microSv/hr (7 to 19 mrem/hr). The total-body effective half-life for these patients ranged from approximately 40 to 88 hr. Using the NRC method and not accounting for the attenuation of photons, the mean dose equivalent to the public exposed to an 131I anti-B1 patient discharged without hospitalization was 4.9 +/- 0.9 mSv (490 +/- 90 mrem). The range was 3.2-6.6 mSv (320 to 660 mrem), where 48% of patients would deliver a dose to another individual that is <5 mSv (500 mrem) (i.e., 48% of the patients would be allowed to return home immediately following the infusion). Using the measured dose rate method, the mean dose equivalent to an individual exposed to the same RIT patients was 2.9 +/- 0.4 mSv (290 +/- 40 mrem). The range was 2.0-3.7 mSv (200-370 mrem), where 100% of the estimated effective dose equivalents were <5 mSv (500 mrem). CONCLUSION: Based on calculated and patient-specific exposure data, outpatient RIT with nonmyeloablative doses of 131I should be feasible for all patients under current NRC regulations. Implementing outpatient RIT should make the therapy more widely available and more convenient and should lower patient care costs without exceeding accepted limits for public exposure to radiation.     

Leukaemias and cancers following iodine-131 administration for thyroid cancer

We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).     

False-positive whole-body iodine-131 scan due to intrahepatic duct dilatation

Focal retention of radioactivity in the liver on whole-body 131I scan was interpreted as a metastatic lesion in a patient with well-differentiated thyroid cancer. Intrahepatic duct dilatation, usually resulting from biliary tract obstruction by bile stone, is a common disorder and may cause bile stasis. A patient with papillary thyroid cancer and a previous history of biliary tract stones had focal retention of radioactivity in the liver on whole-body 131I scan. Abdominal CT, endoscopic retrograde cholagiopancreatography, radionuclide cholangiography and sequential 131I scans demonstrated that this focal retention of radioactivity was caused by intrahepatic duct dilatation. Focal retention of radioactivity is visualized on delayed images but not on early images. The radioactivity initially increases and then decreases on following days.     

Energy-based scatter corrections for scintillation camera images of iodine-131

The use of high-dose 131I antibody therapy requires accurate measurement of normal tissue uptake to optimize the therapeutic dose. One of the factors limiting the accuracy of such measurements is scatter and collimator septal penetration. This study evaluated two classes of energy-based scatter corrections for quantitative 131I imaging: window-based and spectrum-fitting. METHODS: The window-based approaches estimate scatter from data in two or three energy windows placed on either side of the 364-keV photopeak using empirical weighting factors. A set of images from spheres in an elliptical phantom were used to evaluate each of the window-based corrections. The spectrum-fitting technique estimates detected scatter at each pixel by fitting the observed energy spectrum with a function that models the photopeak and scatter, and which incorporates the response function of the camera. This technique was evaluated using a set of Rollo phantom images. RESULTS: All of the window-based methods performed significantly better than a single photopeak window (338-389 keV), but the weighting factors were found to depend on the object being imaged. For images contaminated with scatter, the spectrum-fitting method significantly improved quantitation over photopeak windowing. Little difference, however, between any of the methods was observed for images containing small amounts of scatter. CONCLUSION: Most clinical 131I imaging protocols will benefit from qualitative and quantitative improvements provided by the spectrum-fitting scatter correction. The technique offers the practical advantage that it does not require phantom-based calibrations. Finally, our results suggest that septal penetration and scatter in the collimator and other detector-head components are important sources of error in quantitative 131I images.     

A comparative study of simple methods to measure regional cerebral blood flow using iodine-123-IMP SPECT

The aim of this study was to compare the accuracy and reliability of simple methods of quantifying regional cerebral blood flow (rCBF) with 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) and SPECT and to determine which method was best. METHODS: Four methods were examined: (a) the microsphere method with continuous withdrawal of arterial blood, which was based on a microsphere model using the SPECT image obtained 5 min after tracer injection, (b) the microsphere method with one-point sampling, which was the same as the first method except that one-point sampling was used instead of continuous withdrawal, (c) the modified microsphere method with one-point sampling, which was the same as the second method except that a later SPECT image (30-min postinjection) with correction was used and (d) a table look-up method based on a two-compartment model with one-point arterial blood sampling and two SPECT scans obtained 40- and 180-min postinjection. The accuracy of these methods was validated by comparing the rCBF values with those obtained by nonlinear least squares fitting analysis based on the two-compartment model in 15 subjects. RESULTS: Regional cerebral blood flow values obtained by the first method correlated most closely with those obtained by nonlinear least squares fitting analysis (error, 6.8%). The second method estimated rCBF with a mean error of 10.4%. The third method estimated rCBF with a mean error of 13.1%, even though it tended to slightly overestimate rCBF. The fourth method was inclined to underestimate rCBF with a mean error of 17.1%, and it greatly overestimated regional distribution volume. CONCLUSION: The first method was the most accurate and reliable. For less invasiveness, the first method should be combined with one-point sampling instead of continuous withdrawal, which was used in the second method. When using a delayed SPECT image with a conventional SPECT scanner, the third method was considered to be superior to the fourth method.     

Radioimmunotherapy of medullary thyroid cancer with iodine-131-labeled anti-CEA antibodies

This study evaluates the pharmacokinetics, dosimetry, toxicity and therapeutic potential of radiolabeled NP-4 and MN-14 anti-CEA antibodies in medullary thyroid cancer (MTC). METHODS: Eighteen patients with advanced MTC entered exploratory clinical studies with therapeutic doses of 131I-labeled NP-4 and MN-14 murine monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). Doses administered ranged from 46 mCi for 131I-MN-14 lgG to 195 mCi for 131I-MN-14 F(ab)2 in patients negative for human anti-mouse antibodies (HAMA). RESULTS: The radioconjugate blood half-life (T1/2) for the whole lgG was 42.5+/-5.0 hr compared to 18.8+/- 4.1 hr for the bivalent fragments. Tumor doses of 17.5+/-11.0 and 11.4+/-6.3 cGy/mCi were estimated for 131I-MN-14 lgG and F(ab)2, respectively. Tumor/red marrow dose ratios exceeded 3:1 for most lesions. Red marrow doses of up to 350 cGy generally could be delivered with < grade 4 toxicity. Seven of 14 evaluable patients showed evidence of anti-tumor effects lasting up to 26 months, based on physical exam, tumor markers or computed tomography. CONCLUSION: This study demonstrates that anti-CEA MAbs may be suitable for radioimmunotherapy of metastatic or recurrent MTC.     

Super-early iodine-123-iodoamphetamine SPECT imaging of human primary motor cortex

This study was designed to visualize the motor function area related to finger movements in normal human brain using super-early (first 640 sec of acquisition) [123l]iodoamphetamine ([123I]IMP) SPECT. METHODS: Seven healthy male volunteers performed paired, isolated baseline and task sessions. The task was a right thumb-to-fingers opposition task, which was loaded for the initial 11 min of the session. A high-performance, four-head SPECT camera was used. At each session, administration of 222 MBq [123I]IMP was followed by 16 serial 160-sec dynamic SPECT acquisitions. To obtain matched brain anatomical images, MRI was also performed using the same slice formation as in the SPECT study. After image reconstruction, ROIs were set on bilateral sensorimotor hand areas (SMHA), the supplementary motor area (SMA), the frontal, temporal and occipital lobes and the cerebellar hemispheres. The percent increase of ROI activity (%INC) in the task session compared with that in the baseline session was calculated in each ROI after normalization to the global brain radioactivity. RESULTS: There was significant activation of the left SMHA by the task, the amplitude of which was maximal in the initial phase of dynamic images (the super-early phase). This area was located in the left peri-central area identified on the analogous slice in the MR image. The left SMHA showed gradual and statistically significant decrease of %INC during the three phases. CONCLUSION: Super-early [123I]IMP may be used to identify the primary motor cortex and to evaluate its function in some pathological conditions.     

Crossed cerebellar diaschisis: analysis of iodine-123-IMP SPECT imaging

The aim of this study was to review the etiology of CCD and study factors that affect the development and manifestation of CCD. METHODS: Three hundred and eleven patients with supratentorial lesions were evaluated for the presence of CCD with SPECT and 123I-IMP. In representative cases, continuous arterial blood sampling was done and rCBF was calculated using Kuhl's method. RESULTS: IMP-SPECT detected an abnormality in 206 patients, of whom 30 had CCD. Of CCD patients, 27 had more than single lobe involvement, 17 had motor impairment, 8 of 11 had rCBF of less than 29.1 +/- 10.9 ml/100 g/min. There was also a significant difference in rCBF between non-CCD and CCD cases. CONCLUSION: Although CCD can also occur with dementia (mixed or vascular type), it is more common with multilobar lesions. It is also associated with the presence of motor impairment but not related to its severity. It is more likely to develop, however, if rCBF is less than 29.1 +/- 10.9 ml/100 g/min regardless of etiology.     

Breast cyst simulating metastases on iodine-131 imaging in thyroid carcinoma

False-positive radioiodine uptake has been reported in many organ systems. We describe a female patient who had mixed papillary and follicular thyroid carcinoma, and on radioiodine total-body imaging demonstrated focal, lower-right chest uptake. Special prone imaging with the right breast dependent proved that the uptake was inside the right breast. Review of a recent breast ultrasound and mammograms showed this uptake to correspond to a large breast cyst. It is known that 131I breast uptake may be functional within the mammary gland. In this patient, it was due to retention within the cyst after the background activity decreased. Knowledge of this phenomenon may improve the interpretation of total-body 131INa studies.     

Age-related changes in D2 receptor binding with iodine-123-iodobenzofuran SPECT

The purpose of this study was to evaluate the effects of age on D2 receptor binding with 123I-iodobenzofuran (IBF) SPECT. METHODS: Subjects were 40 healthy volunteers (age 19-83 yr), including 6 who had test/retest studies. Scans were acquired with a triple-head SPECT camera 3 hr postinjection of IBF (300 MBq). Striatal regions (caudate and putamen) were defined by two different region-of-interest (ROI) sets consisting of large volumes [(CLVs), 2.2 and 6.6 m] and small volumes [(SVs), 0.6 and 1.3 ml]. D2 binding (Rv=V3/V2) was quantified using our previously proposed multilinear regression technique. Effects of age on D2 binding were evaluated by fitting linear, exponential and logarithmic models. RESULTS: The mean Rvs were 26% lower than LV for both putamen and caudate than the corresponding values from the SV due to the partial-volume effect. Although the identifiability of Rv using SV deteriorated slightly, the test/retest reproducibility of Rv measurements was equally excellent for LV and SV. The mean Rvs were 11% higher for putamen compared with those for caudate. D2 binding declined significantly with age (p < 10(-5)) for all three models. The nonlinear models were slightly superior to the linear model in describing the relationship between Rv and age. In these models, D2 binding declined with age, equally for caudate and putamen at 7%-13% per decade; the decline was progressively smaller with age. CONCLUSION: IBF SPECT permitted reliable measurements of D2 binding in the caudate or putamen separately using small ROI volumes that significantly improved the quantitation loss from the partial-volume effect. Our results agreed with previous PET and postmortem findings of D2 binding losses with age. However, these age effects may be nonlinear. Age-related changes in D2 binding must be taken into consideration in clinical IBF SPECT investigations.     

Post-therapy iodine-131 localization in unsuspected large renal cyst: possible mechanisms

Sensitive and specific, whole-body 131I scintigraphy remains an important technique for diagnosing metastases from differentiated papillary or follicular thyroid carcinoma. False-positive 131I localization is well recognized and can occur in a variety of conditions. We present a case of intense 131I localization in a previously unsuspected large renal cyst; the lesion was not visualized on routine preablation diagnostic 131I scintigraphy but was obvious on post-therapeutic whole-body imaging, underscoring the value of post-therapy imaging in detecting abnormalities not apparent on diagnostic studies. Radioiodine within the urinary bladder or, at times, the renal collecting system is expected, because 131I excretion is primarily by glomerular filtration. In the case presented here, 131I activity within the renal cyst supports the concept that iodide is subject to an active secretory process by the renal tubule.     

Iodine-123-iomazenil and iodine-123-iodoamphetamine SPECT in major cerebral artery occlusive disease

Iodine-123-iomazenil (IMZ) is a SPECT ligand for central-type benzodiazepine receptors, which are located only on neurons. We evaluated the feasibility of using IMZ SPECT for identifying neuronal damage in patients with the chronic phase of thrombotic cerebral ischemia. METHODS: We studied 15 patients with angiographically-confirmed unilateral severe occlusive lesions (occlusion or > 70% stenosis) in the carotid system. IMZ SPECT images obtained 180 min after injection of 167-222 MBq IMZ were analyzed. The regional cerebral blood flow and perfusion reserve were evaluated for comparison with IMZ SPECT findings, using the split-dose 123I-iodoamphetamine (IMP) SPECT method, coupled with intravenous injection of 1 g acetazolamide. On both SPECT images, the count ratio of the affected to the nonaffected whole MCA territory (A/NA ratio) and of the contralateral to the ipsilateral cerebellar cortex (C/I ratio) were determined. RESULTS: The A/NA ratio with IMZ was significantly higher than that with IMP (94.5% +/- 6.2% versus 91.4% +/- 6.6%, p < 0.005), although a significantly positive correlation was found between these two ratios (r = 0.854, p < 0.0001). The C/I ratio with IMP was decreased significantly in 5 patients compared with that in normal subjects, whereas the C/I ratio with IMZ was decreased in only 1 patient. There was no significant correlation between the A/NA ratio with IMZ and the perfusion reserve in the affected MCA territory. In 2 of 5 patients with a decreased A/NA ratio (<90%) with IMZ, decreased blood flow with preserved perfusion reserve and cerebral hemispheric atrophy were observed, which suggested the influence of neuronal loss due to chronic ischemia. CONCLUSION: These findings indicate that IMZ SPECT, which provides new information regarding neuronal damage after ischemic insult to the brain, is useful for evaluating thrombotic cerebral ischemia.