Ernst G. Eising

Optimized 124I PET Dosimetry Protocol for Radioiodine Therapy of Differentiated Thyroid Cancer

Iodine kinetics and lesion dose per administered 131I activity (LDpA) of differentiated thyroid cancer metastases were determined using 124I PET. These data were analyzed to derive an optimized dosimetry protocol. Methods: We evaluated the time-activity-concentration curves of 37 lesions in 17 patients who had undergone thyroidectomies. LDpA determination involved 124I PET images acquired at 4, 24, 48, 72, and 96 h after intake of a capsule containing 20–40 MBq of 124I. A combination of a linear and a monoexponential or a monoexponential function only parameterized the time-activity-concentration curves. The LDpAs, calculated using data from all 5 PET time points, served as reference. The lesions were classified into 3 groups, according to potential for cure with 131I therapy: low (≤5 Gy GBq−1; n = 14), medium (between 5 and 10 Gy GBq−1; n = 9), or high LDpAs (>10 Gy GBq−1; n = 14). Using the reference approach, the differences in the empiric kinetic parameters within the LDpA groups were evaluated. The reference LDpAs were compared with those derived from only 2, 3, or 4 PET data points and from 1 adapted 2-point approach. Lins concordance correlation coefficient (ρc) and the mean absolute percentage deviation in LDpAs were used to assess agreement between simplified and reference approaches. Results: The effective 124I half-life, linear activity–concentration rate (α), and 24-h activity concentration (CpA) (the latter 2 per administered 124I activity) differed significantly among the LDpA groups (P < 0.05). LDpAs correlated with 24-h CpAs (r = 0.94, P < 0.001). Using the 4-, 24-, and 96-h measurements, a ρc value of greater than or equal to 0.90 was found, and the mean absolute percentage deviation was less than or equal to 16%. Similar statistical values were obtained for the adapted approach, which was based on 24- and 96-h PET data points only. Conclusion: Lesion classification into LDpA groups was feasible using a single PET scan at ∼24 h. Because of the highly variable kinetics, 1 additional measurement at ∼96 h was needed to obtain a sufficiently reliable LDpA estimate. The adapted 24-96-h approach appears to be the optimal 124I protocol and is a reliable simplification of the 5-point protocol.

Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer.

AimTo estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy. MethodsFifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1–21 GBq 131I using single activities of 1–6 GBq. The patients were stratified according to the cumulative activities into low-activity (1–2 GBq), middle-activity (3–7 GBq), and high-activity groups (9–21 GBq). The time–activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models. ResultsThe median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy·GBq−1 (range, 0.1–0.3 Gy·GBq−1) and 0.48 Gy·GBq−1 (range, 0.2–1.2 Gy·GBq−1), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups. ConclusionThe iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered 131I activity was not significantly decreased during the course of therapy. Comparing the well-known dose–effect relationships in external radiation therapy, the absorbed dose per administered 131I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of 131I in human salivary glands.

Non-invasive characterization of cardiac microvascular disease by nuclear medicine using single-photon emission tomography.

In about 10 to 30% of patients with typical angina undergoing coronary angiography for suspicion of stenotic coronary artery disease angiographically normal coronary arteries are found. Kemp et al. in 1973 coined the term syndrome X to describe this entity. In a substantial portion of these patients pathologic findings in myocardial scintigraphy are present.Sensitivity and specificity of thallium-201 exercise imaging by visual analysis of images in the presence of significant coronary stenosis is 84 and 88%, respectively. Several investigators have reported abnormal results in radionuclide exercise tests in patients with angiographically normal coronary arteries. Some of these results can be explained by myocardial bridging, vasospasm, left or right bundle branch block, hypertrophic cardiomyopathy, or absorption artifacts. In the majority of cases, however, these abnormalities are not sufficient to explain the scintigraphic findings. Formerly often claimed “false positive”, recent studies suggest that endothelial dysfunction might be the reason for the observed perfusion defects. When comparing patients with angiographically unobstructed coronary arteries with and without perfusion defects in stress myocardial perfusion imaging, patients with pathological results show a significantly lower increase of coronary flow after intracoronary injection of the endothelialdependent vasodilator acetylcholine. Endothelial-independent vasodilation, however, is not impaired in these patients. In addition, intracoronary Doppler measurements reveal that perfusion defects in myocardial scintigraphy only occur if coronary blood flow in this perfusion area is significantly reduced. These results suggest that regional endothelial dysfunction may cause hypoperfusion in myocardial perfusion imaging and underline the important role of the microcirculation in the distribution of radiotracers.Another striking scintigraphic pattern in patients with microvascular angina is the high incidence of reverse redistribution. These perfusion defects, apparent in images obtained 4 hours after exercise stress testing, often cannot be assigned to the perfusion territory of one of the major epicardial vessels. This results in a marked inhomogeneous radionuclide distribution pattern in resting images. The inhomogeneity is associated with a significant reduced resting coronary flow velocity in these patients. As histologically confirmed microvessel disease is often accompanied by slow-flow phenomenon reflecting decreased resting flow velocity, the results suggest that the inhomogeneous perfusion pattern is caused by microvascular dysfunction. Furthermore, the heterogeneity of nuclide distribution supports the hypothesis that endothelial function is not homogeneous in the entire myocardial microcirculation, but varies considerably.In conclusion, microvascular dysfunction by itself seems to cause regional myocardial hypoperfusion, as documented by myocardial scintigraphy. When interpreting pathological scintigraphic results in patients without significant epicardial stenosis, true blood flow and myocardial perfusion abnormalities must be assumed.ZusammenfassungIn der diagnostischen Koronarangiographie zeigen 10 bis 30% der untersuchten Patienten mit typischer pektanginöser Beschwerdesymptomatik nichtstenosierte Koronararterien. Bei einem großen Anteil der Patienten läßt sich in der Myokardszintigraphie jedoch ein pathologischer Befund erheben. Kemp hat 1973 für die Entität aus angiographisch normalen epikardialen Gefäßen, Angina pectoris und positivem Ischämienachweis den Begriff Syndrom X geprägt.Die Myokardszintigraphie stellt ein weit verbreitetes und gut validiertes Verfahren in der Funktionsdiagnostik der koronaren Herzerkrankung dar. Die Sensitivität und Spezifität der [201Tl] Thalliumchlorid-Szintigraphie im Hinblick auf eine signifikante epikardiale Stenose werden in Abhängigkeit von der Untersuchungstechnik mit 84 und 88% angegeben. Minderanreicherungen können außer durch höhergradige Stenosierungen der Koronargefäße bei Muskelbrücken, Koronarspasmen, beim Links- und Rechtsschenkelblock auftreten, aber auch aufgrund von Absorptionsartefakten vorgetäuscht werden. Werden oben genannte Ursachen für Perfusionsdefekte ausgeschlossen, so lassen sich dennoch bei Patienten mit Angina pectoris häufig pathologische Befunde erheben. Während Perfusionsdefekte in der Myokardszintigraphie bei Patienten mit angiographisch unauffälligen Koronararterien zunächst als „falsch positiv” gewertet wurden, deuten neuere Studienergebnisse darauf hin, daß diesen szintigraphischen Minderbelegungen eine endotheliale Dysfunktion der myokardialen Mikrozirkulation ursächlich zugrunde liegt. Werden Patienten mit angiographisch nicht stenosierten Koronararterien mit und ohne Perfusionsdefekte unter Belastung in der201TlCl-Myokardszintigraphie verglichen, so weisen Patienten mit pathologischem Belastungsszintigramm einen signifikant geringeren Anstieg des koronaren Flusses auf die Gabe des endothelabhängigen Vasodilatators Acetylcholin auf. Die endothelunabhängige Vasodilatation auf Papaverin ist hingegen in beiden Gruppen gleich. Wie intrakoronare Doppler-Messungen zeigen konnten, treten regionale Perfusionsdefekte in der Myokardszintigraphie nur dann auf, wenn ein signifikant reduzierter relativer Blutfluß in dem jeweiligen Myokardareal besteht. Diese Ergebnisse unterstreichen die wichtige Rolle der Mikrozirkulation für die Nuklidverteilung in der Myokardszintigraphie. Neben belastungsinduzierten regionalen Minderperfusionen zeigen Patienten mit nichtstenosierten Koronararterien und Angina pectoris häufig auch eine inhomogene Nuklidverteilung in Ruhe, welche unter Belastung nicht besteht. Dieses Phänomen tritt meist unabhängig vom Versorgungsgebiet der großen epikardialen Gefäße auf. Intrakoronare Doppler-Messungen zeigten, daß dieses inhomogene Verteilungsmuster mit einer reduzierten koronaren Flußgeschwindigkeit in den epikardialen Gefäßen einhergeht. Ähnliche Ergebnisse wurden in einem Kollektiv von herztransplantierten Patienten erhoben, die eine progressive Inhomogenität des Nuklidverteilungsmusters in der201TlCl-Myokardszintigraphie in Abhängigkeit von der Dauer nach Transplantation aufwiesen. Da weder angiographisch noch im intravaskulären Ultraschall signifikante Stenosierungen gefunden wurden, wird hier eine Störung der Mikrozirkulation im Rahmen einer Transplantatvaskulopathie als Ursache diskutiert.Zusammenfassend kann daher festgestellt werden, daß pathologische Ergebnisse in der Myokardszintigraphie bei Patienten mit angiographisch nichtstenosierten epikardialen Gefäßen real existierende Minderperfusionen widerspiegein. Nach den vorliegenden Untersuchungen sind diese durch regional begrenzte Störungen der myokardialen Mikrozirkulation bedingt. Ein Charakteristikum dieser durch eine Störung der Mikrozirkulation bedingten Perfusionsmuster scheint eine inhomogene Nuklidverteilung in den Redistributionsaufnahmen zu sein.

SPECT imaging with [123i]-β-CIT in Parkinsonism : comparison of SPECT images obtained by a single-headed and a three-headed gamma camera

Single photon emission computed tomography (SPECT) imaging of dopamine transporters by using the cocaine derivative [123I]-(1R)-2-β-carbomethoxy-3-β-(4-iodophenyl)-tropane ([123I]-β-CIT) has been shown to be useful in patients with Parkinsonism. The aim of this study was to compare β-CIT imaging with single-headed (SHS) and three-headed gamma camera systems (THS). In 17 patients with Parkinsonism, SPECT imaging with an SHS and a THS was performed 24 h after injection of 180 MBq of [123I]-β-CIT. The SPECT studies were evaluated by visual assessment of the caudate nucleus (CN) and the putamen (PT) and the calculation of the striatal/cerebellar (S/C) ratios (with additional comparison to clinical symptoms measured by the Unified Parkinsons Disease Rating Scale (UPDRS)). The S/C ratios measured by the SHS and THS showed highly significant correlation (two-tailed P<0.01) with Spearman correlation coefficients (SCCs) of 0.864 for the right side, 0.676 for the left side, and 0.761 for both sides. By the SHS, a sufficient visual differentiation between the CN and the PT could not be achieved. A significantly better distinction could be achieved by using the THS (Wilcoxon P<0.05). The S/C ratios of the THS only showed a significant (P<0.05) SCC of −0.514 comparing to the UPDRS. Pathological alterations in the β-CIT uptake pattern could be identified by using the SHS, but a significantly better differentiation of CN and the PT was possible by using the THS. The significant correlation of the S/C ratios measured by THS only emphasizes the value of THS in β-CIT imaging.

Influence of various geometric factors on the iodine-131 uptake measurement for solitary thyroid nodules.

AimThe influence of various geometric factors on 131I uptake measurements for solitary thyroid nodule was systematically investigated to derive an approach, based on routinely performed ultrasound examinations, to correct for the effect of geometric variations. MethodsThe influence of size, shape, and position of a thyroid nodule, neck-to-detector distance and neck curvature on the uptake value was analyzed with a three-dimensional model. Uptake measurements using a tissue-equivalent neck phantom were carried out to verify the calculated correction factors and also to check the influence of scatter. Sonograms of 92 patients with solitary nodules were analyzed to correct for geometric variations. ResultsThe correction factors were independent of the size and shape of the nodule, and the activity distribution of the solitary nodules can be approximated by a point source. The correction factors were mainly determined by the nodular depth and by the accuracy of the neck-to-detector distance and were affected to a lesser extent by the lateral position of the nodule as well as the curvature of the neck. The effect of scatter can be neglected if the energy window largely excludes Compton scatter, as is the case in the 131I uptake measurement. The ultrasound-derived correction factors ranged from 0.85 to 1.25. ConclusionThe proposed approach is capable of correcting for the geometric variation for a solitary nodule and can be easily applied in routine clinics. The accuracy of absorbed dose in radioiodine therapy can be improved in particular for nodules located well beneath the neck surface.