This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates.

https://jnm.snmjournals.org/content/jnumed/40/2/37S.full.pdf

MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates.

Ischemic renal disease: An overlooked clinical entity?

On-board imager (OBI) based cone-beam computed tomography (CBCT) has become available in radiotherapy clinics to accurately identify the target in the treatment position. However, due to the relatively slow gantry rotation (typically about 60 s for a full 360° scan) in acquiring the CBCT projection data, the patient's respiratory motion causes serious problems such as blurring, doubling, streaking and distortion in the reconstructed images, which heavily degrade the image quality and the target localization. In this work, we present a motion compensation method for slow-rotating CBCT scans by incorporating into image reconstruction a patient-specific motion model, which is derived from previously obtained four-dimensional (4D) treatment planning CT images of the same patient via deformable registration. The registration of the 4D CT phases results in transformations representing a temporal sequence of three-dimensional (3D) deformation fields, or in other words, a 4D model of organ motion. The algorithm was developed heuristically in two-dimensional (2D) parallel-beam geometry and extended to 3D cone-beam geometry. By simulations with digital phantoms capable of translational motion and other complex motion, we demonstrated that the algorithm can reduce the motion artefacts locally, and restore the tumour size and shape, which may thereby improve the accuracy of target localization and patient positioning when CBCT is used as the treatment guidance.

http://iopscience.iop.org/article/10.1088/0031-9155/51/2/005/pdf

Motion correction for improved target localization with on-board cone-beam computed tomography

Attenuation compensation for cardiac single-photon emission computed tomographic imaging: Part 1. Impact of attenuation and methods of estimating attenuation maps

The purpose of this study was to determine the frequency with which a mosaic pattern of lung attenuation is seen on chest CT scans in patients with various causes of pulmonary artery hypertension (PAH).Chest CT scans of 64 patients with known PAH were reviewed to assess the patterns of lung attenuation. Patterns of lung attenuation were divided into three categories: class I, homogeneous lung parenchymal attenuation; class II, slightly heterogeneous lung attenuation that does not conform to the anatomic boundaries of the secondary pulmonary lobule; and class III (mosaic pattern), heterogeneous lung attenuation in geographic regions with well-defined borders corresponding to the anatomic units of single or multiple secondary pulmonary lobules. The patients medical histories were reviewed to determine the primary cause of PAH for each patient.Peak pulmonary artery pressure of the patients in our study averaged 74 mm Hg (range, 36-194 mm Hg). Twenty-one patients had PAH due to lung disease: 17 patients, due ...

Mosaic pattern of lung attenuation on CT scans: frequency among patients with pulmonary artery hypertension of different causes.

Radionuclide transmission CT generated on a rotating gamma camera can improve SPECT imaging by providing attenuation maps for attenuation compensation and for anatomical correlation. This paper demonstrates the feasibility and high quality of cone-beam transmission CT (CB-CT) of human subjects, in comparison to conventional parallel-ray CT, and evaluates some possible imaging protocols. Two CB-CT implementation modes, with a cone-beam collimator and without any collimator, were evaluated. Three human subjects of different dimensions were imaged. For the two smaller subjects, the CB-CT images were dramatically superior, in terms of noise and resolution, to those obtained with a parallel-ray geometry. The image noise was less by a factor of 6. CB-CT linear attenuation coefficients were found to be in close agreement with published values for various tissues. For the largest subject, image truncation produced a ring artifact at the edge, but inside the artifact, the image quality was still very good. Cone-beam images obtained without any collimator were acceptable, but photon scatter degraded the image contrast.

http://jnm.snmjournals.org/content/33/1/150.full.pdf

Imaging of the human torso using cone-beam transmission CT implemented on a rotating gamma camera.

Increased renal uptake of 99mTc methylene diphosphonate (MDP) was observed irregularly in rats after methotrexate, vincristine or gentamicin, administered separately. Cisplatin regularly induced a dose-related increased MDP uptake which correlated with the degree of tubular damage histologically. The augmented MDP renal uptake was not consistently accompanied by a decreased clearance of simultaneously injected I-131 Hippuran, particularly at lower drug dose levels. This observation agreed with previous evidence that the mechanisms of tubular transport of diphosphonates and organic acids like Hippuran are different. At higher dose levels, the augmented MDP uptake was accompanied by increased renal calcium, hypophosphatemia, elevated serum urea nitrogen and creatinine, and only occasional, mild hypercalcemia. The magnitude of the increased renal uptake of MDP observed could not be explained by alterations in iron metabolism or by dehydration. Drug-induced renal retention of MDP by a factor of 2 or more above normal appears to be a useful indicator of tubular damage when other parameters of renal function are sometimes normal.

Experimental drug-induced changes in renal function and biodistribution of 99mTc-MDP.

A recently developed 1-day screening procedure for angiotensinogenic ("high-renin") hypertension is based on (A) a fall in blood pressure in response to intravenous infusion of the angiotensin antagonist, saralasin (P-113), and (B) peripheral venous renin assays by radioimmunoassay, in a sodium-depleted state. Out of 700 hypertensive patients screened by these tests, 160 had renal imaging performed with technetium-99m glucoheptonate and iodine-131 Hippuran. The P-113 infusion test proved superior to peripheral venous renin assays for the detection of angiotensinogenic hypertension. Positive infusion tests correlated well with renal vein renin assays. Frequently, however, both these tests were positive with bilateral renal disease and/or malignant hypertension. While renal imaging proved valuable in indicating which patients had a unilateral abnormality, it frequently could not distinguish unilateral renovascular disease from unilateral parenchymal disease unrelated to angiotensinogenic hypertension. Twenty-five patients in this series had arteriographic renal artery stenosis, of whom 3 had false negative P-113 infusion tests, 9 had negative peripheral renin assays, and 3 had no imaging abnormalities. This study indicates that scintigraphy is a useful procedure for the investigation of hypertensive patients when the initial P-113 infusion test is positive, or discordant with other findings. By imaging, angiotensinogenic hypertension due to bilateral renal disease can be distinguished from unilateral renovascular disease, and the site of the ischemic renal tissue can usually be identified.

Diagnosis of Angiotensinogenic Hypertension: The Complementary Roles of Renal Scintigraphy and the Saralasin Infusion Test

The 3-hour biodistribution of 99mTc complexes of five diphosphonates (HMDP, NMMDP, DMAD, DPD, and APD), imidodiphosphonate (IDP), and pyrophosphate (PYP) was compared in rats with segmental renal infarction induced by a 1-hour occlusion of a renal artery branch. 95mTc labeled MDP was a reference substance in all animals. Three agents (APD, HMDP and IDP) had a higher infarct/normal kidney concentration ratio than MDP, the latter two by virtue of a lower content in normal kidney. HMDP, DPD, and IDP had very high liver concentrations. DPD showed relatively high concentrations in soft tissues and blood. The blood and kidney levels of PYP were higher than those of MDP but the infarct/normal kidney ratios were similar. None of the agents had a higher uptake in bone than MDP: four had a significantly lower uptake. The increased concentration of 99mTc MDP in the infarcts was readily seen in camera images one day after renal artery occlusion, but not at three or seven days. Increased diphosphonate uptake was accompanied by an influx of calcium in both cortex and medulla. The accumulation of diphosphonate in areas of infarction was not modified by infusions of verapamil or Captopril.

Comparison of 99mTc phosphate and diphosphonate complexes in experimental renal infarcts.

Successful identification of oligemic lung by transmission computed tomography after experimentally produced acute pulmonary arterial occlusion in the dog.

Thomas Fd

Papers

Imaging of the human torso using cone-beam transmission CT implemented on a rotating gamma camera.

Experimental drug-induced changes in renal function and biodistribution of 99mTc-MDP.

Diagnosis of Angiotensinogenic Hypertension: The Complementary Roles of Renal Scintigraphy and the Saralasin Infusion Test

Comparison of 99mTc phosphate and diphosphonate complexes in experimental renal infarcts.

Successful identification of oligemic lung by transmission computed tomography after experimentally produced acute pulmonary arterial occlusion in the dog.