[en] The issue of The Journal of Nuclear Medicine contains three articles representing advances in emission tomography instrumentation. Common to all three designs is the goal of acquiring volumetric data with good sampling in three dimensions. There are two motivations leading to the volumetric data acquisition. First there is a physiologic and clinical need to take into account the complex nature of the organ such as the brain in x, y, and z directions. Secondly, there is an argument that improved sensitivity will come from systems whose detectors can acquire data from a larger solid angle than provided by positron emission tomography (PET) instrument design with single crystal detector units and septal shields between layers. This editorial is written to serve three purposes: (1) to highlight the distinguishing features of these three instrumentation papers (2) to present quantitative comparisons between the single-photon emission computed tomography (SPECT) and PET instruments (3) to forecast some ideas for the future developments in both SPECT and PET

[en] The authors report a case of rapid ^99mTc-methoxyisobutylisonitrile (MIBI) clearance from a parathyroid adenoma. A double-phase ^99mTc-MIBI parathyroid scintigraphy was performed on a 62-yr-old female evaluated for primary hyperparathyroidism. A large parathyroid adenoma was visualized caudal to the left lobe of the thyroid gland with an unusually rapid washout of the tracer from tumor tissue. Histologic tissue examination confirmed the presence of a parathyroid adenoma and the absence of oxyphil cells. Care should be taken in interpretation of ^99mTc-MiBI parathyroid scintigrams because some adenomas can present a rapid release of the radiotracer in a double-phase study. Technitium-99m-MIBI retention could be related to the number of mitochondria-rich cells in parathyroid adenomas or to hyperplasia. 7 refs., 2 figs

[en] The aim of the present study was to assess whether ¹³¹I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7±54 mo (range 10-243 mo). Mean FSH values in ¹³¹I-treated patients tested after their last treatment were 15.3±9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5±3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients had an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to ¹³¹I therapy was not universal. Six patients had no change or a slight increase in serum FSH after ¹³¹I administration; eleven patients had a transient increase above normal values 6-12 mo after ¹³¹I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several ¹³¹I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. The results indicate that ¹³¹I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility. 14 refs., 8 figs., 1 tab

[en] Four dogs with histologically confirmed osteogenic sarcoma were studied with PET following intravenous injection of the ¹⁸F-labeled Fab fragment of TP-3, a monoclonal antibody specific for human and canine osteosarcomas. The antibody fragment was labeled using the N-succinimidyl (8-(4'-(¹⁸F)fluorobenzyl)amino)suberate acylation agent. Blood clearance of activity was biphasic in all dogs but half-times were variable (T_1/2β = 2-13 hr). Catabolism of labeled Fab was reflected by the decrease in protein-associated activity in serum from more than 90% at 1 min to 60%-80% at 4 hr. PET images demonstrated increased accumulation of ¹⁸F at the primary tumor site relative to normal contralateral bone in one dog as early as 15 min after injection. Biopsies obtained after euthanasia indicated higher uptake at the edges of the tumor as observed on the PET scans. Tumor uptake was 1-3 x 10^-3% injected dose/g, a level similar to that reported for other Fab fragments in human tumors. In the three dogs with metastatic disease, early PET images reflected activity in the blood pool but later uptake was observed in suspected metastatic sites. These results, although preliminary, suggest that PET imaging of ¹⁸F-labeled antibody fragments is feasible and that dogs with spontaneous tumors could be a valuable model for preclinical research with radioimmunoconjugates. 34 refs., 6 figs., 2 tabs

[en] The internal dosimetry schema of the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine has provided a broad framework for assessment of the absorbed dose to whole organs, tissue subregions, voxelized tissue structures, and individual cellular compartments for use in both diagnostic and therapeutic nuclear medicine. The schema was originally published in 1968, revised in 1976, and republished in didactic form with comprehensive examples as the MIRD primer in 1988 and 1991. The International Commission on Radiological Protection (ICRP) is an organization that also supplies dosimetric models and technical data, for use in providing recommendations for limits on ionizing radiation exposure to workers and members of the general public. The ICRP has developed a dosimetry schema similar to that of the MIRD Committee but has used different terminology and symbols for fundamental quantities such as the absorbed fraction, specific absorbed fraction, and various dose coefficients. The MIRD Committee objectives for this pamphlet are 3-fold: to restate its schema for assessment of absorbed dose in a manner consistent with the needs of both the nuclear medicine and the radiation protection communities, with the goal of standardizing nomenclature; to formally adopt the dosimetry quantities equivalent dose and effective dose for use in comparative evaluations of potential risks of radiation-induced stochastic effects to patients after nuclear medicine procedures; and to discuss the need to identify dosimetry quantities based on absorbed dose that address deterministic effects relevant to targeted radionuclide therapy.

[en] N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β(4-chlorophenyl)tropane (IPT) is an analog of cocaine that selectively binds the presynaptic dopamine transporter. The present study sought to measure the radiation dosimetry of IPT in seven healthy human volunteers. Dynamic renal scans were acquired immediately after the intravenous administration of 165 ± 16 MBq (4.45 ± 0.42 mCi) of [¹²³I]IPT. Between 7 and 12 sets of whole-body scans were acquired over the next 24 hr. The 24-hr renal excretion fractions were measured from conjugate emission scans of 7-11 discreet voided urine specimens. The fraction of the administered dose in 11 organs and each urine specimen was quantified from the attenuation-corrected geometric mean counts in opposing views. Subject-specific residence times were evaluated for each subject independently by fitting the time-activity curves to a multicompartmental model. The radiation doses were estimated with the MIRD technique from the residence times for each subject individually before any results were averaged. The findings showed that IPT was excreted rapidly by the renal system. There were no reservoirs of retained activity outside the basal ganglia, where SPECT images in these subjects showed that the mean ratio of caudate to calcarine cortex averaged 25:1 at 3 hr after injection (range 19.6-32 hr). The basal ganglia received a radiation dose of 0.028 mGy/MBq (0.10 rad/mCi). The dose-limiting organ in men was the stomach, which received an estimated 0.11 mGy/MBq (0.37 rad/mCi). In women, the critical organ was the urinary bladder at 0.14 mGy/MBq (0.51 rad/mCi). Relatively high-contrast images of the presynaptic dopamine transporters in the basal ganglia can be acquired with 185 MBq (5 mCi) of [¹²³I]IPT. The radiation exposure that results is significantly less than the maximum allowed by current safety guidelines for research volunteers. 33 refs., 4 figs., 3 tabs

[en] The authors evaluated the ability of ^99mTc-hexamethylpropyleneamine oxime (^99mTc-HMPAO) to serve as a sensitive marker of lung injury. Two experiment rabbit models of minimal lung injury were designed using injections of a low dose (0.05 ml/kg) of oleic acid or 50 Gy of irradiation. In addition, they clinically investigated whether patients who received chemotherapy (n = 14) or radiotherapy (n = 13) for lung cancer showed high uptake of ^99mTc-HMPAO in the lungs. Despite the minimal endothelial lesions visualized by electron microscopy (edematous changes and blebbing), in both animal models, the lungs showed high uptake of ^99mTc-HMPAO, which occurred rapidly within 1 min after injection. Clinically, the mean lung-to-liver ratio of ^99mTc-HMPAO activity in the patients who received chemotherapy (0.649±0.185, p < 0.01) was significantly higher than that of the controls (n = 16; 0.387±0.108), and all 12 patients who received more than 30 Gy of irradiation showed abnormal uptake in the irradiated lungs, despite the lack of abnormal opacities on chest CT. These findings suggest that ^99mTc-HMPAO has the potential to be a sensitive marker of chemical and irradiation lung injury. 53 refs., 5 figs., 3 tabs

[en] The effect of a chelator structure on the metabolic fate of the ¹¹¹In-labeled monoclonal antibody (Mab) T101 was investigated in normal Balb/c mice to assess the importance of this chemical parameter in the reduction of the background radioactivity in blood and liver. Mab T101 was conjugated with either 2-(p-isothiocyanatobenzyl)-6-methyl-diethylaminetriaminepentaacetic acid (DTPA) (1B4M), 2-(p-isothiocyanatobenzyl) cyclohexyl-DTPA (CHX-B) or cyclic DTPA dianhydride (cDTPA) and then radiolabeled with ¹¹¹In-labeled T101 conjugates and sacrificed in groups of five up to 5 days postinjection for comparative biodistribution studies and analyses of liver, blood and urine samples for radioindium products. The biodistribution of ¹¹¹In-1B4M-T101 and ¹¹¹In-CHX-B-T101 were similar to each other but significantly different from that of ¹¹¹In-cDTPA-T101, particularly in the blood and liver. Size-exclusion high-performance liquid chromatography indicated that the concentration of the intact ¹¹¹In-immunoglobulin (Ig)G in liver decreased with similar rates for the three conjugates. Meanwhile, the concentration of a small DTPA-like metabolite in liver increased to a different peak value (4.6% 1D/g for the cDTPA conjugate and 1.6% lD/g for the 1B4M and CHX-B conjugates) approximately at 24 hr and maintained a steady-state concentration up to 5 days. The thiourea linkage between T101 and the ¹¹¹In-labeled chelates and a higher complex stability and higher lipophilicity of ¹¹¹In-1B4M and ¹¹¹In-CHX-B appear to be responsible for lower liver and higher blood radioactivity for the 1B4M and CHX conjugates. 31 refs., 3 figs., 1 tab

[en] Two major obstacles in the development of improved methods for more accurate dose estimates for radioimmunotherapy have been the difficulty in obtaining an accurate patient-specific three-dimensional activity map in vivo and calculating the resulting absorbed dose. We propose a method for three-dimensional internal dosimetry that integrates the three-dimensional activity map from SPECT with a dose-point kernal convolution technique to provide the three-dimensional distribution of absorbed dose. Accurate activity quantitation was achieved with appropriate methods. The count density map from SPECT images was converted into an activity concentration map with a calibration phantom approach. This map was then convolved with an ¹³¹I dose-point kernel and three-dimensional fast Fourier transform to yield three-dimensional distribution of absorbed dose, which was then processed to provide the absorbed dose distribution in regions of interest. The accuracy of quantitative SPECT was validated to be within 16%. The calculated penetrating radiation absorbed dose was verified with thermoluminescent dosimeter measurements to be within 8%. With standard organs and configuration, the method calculated absorbed dose in good agreement with the MIRD formalism (less than 14%). This method overcomes the limitations of planar imaging techniques and the current routine implementation of the MIRD formalism. The results can be processed to provide the absorbed dose distribution in regions of interest and parameters for treatment optimization. Absorbed dose distribution from any plane can be graphically displayed in various ways. 53 refs., 9 figs., 3 tabs

[en] Thallous chloride (²⁰¹Tl) is a well-known imaging agent. It has been shown to accumulate in the testes. In view of this, the testicular kinetics of ²⁰¹Tl is investigated in humans and the absorbed dose to the organ calculated. Thallous chloride ²⁰¹Tl was injected intravenously into four patients for myocardial perfusion studies. After clinical evaluation, the testicular uptake and clearance of ²⁰¹Tl were monitored for about 1 wk using a gamma camera. Testicular uptake of ²⁰¹Tl was rapid with a mean biological uptake half-time of 0.67 hr and mean biological clearance half-time of 280 hr. The mean maximum testicular uptake of ²⁰¹Tl was about 0.4% of the injected activity. These data were utilized to calculate the average absorbed dose to the testes. The absorbed dose to the testes was calculated to be 3.5 x 10^-4 Gy/MBq (1.3 rad/mCi) of injected activity. When the relative biological effectiveness of the Auger emitter ²⁰¹Tl is taken into account, the equivalent dose to the testes is 9.5 x 10^-4 Sv/MBq (3.5 rem/mCi). 14 refs., 1 fig., 2 tabs