Frank P. Castronovo

The Clinical Use of 99mTc-Diphosphonate (HEDSPA)

Clinical experience in over 500 patients scanned with 99mTc-diphosphonate is discussed. In comparison with 18F scans and roentgen studies, 99mTc-diphosphonate has produced similar or better studies. Frequently, the diphosphonate scan is more sensitive, especially in the detection of metastases to bone. In addition, calcific soft-tissue deposits and urinary tract pathology have been visualized on 99mTc-diphosphonate scans. Scanning with 99mTc-diphosphonate is considered to be the most effective imaging modality available for determining the presence and extent of skeletal metastases.

Radiation exposure and protection in cardiac catheterization laboratories

Cardiac catheterization with angiography can deliver the greatest dose of x-radiation of any diagnostic medical examination. The physicians and technologists in the angiography room receive low-level scattered radiation over a period of months to decades. Although the radiobiology is complex, the physicians who perform cardiac catheterization should be familiar with the potential genetic and somatic effects of radiation and with the methods to reduce or eliminate x-ray exposure. The aim of radiation protection criteria is to reduce the risk of cancer death to less than the fatality risk for other occupations regarded as safe. This report is a review of the literature relating to radiation exposure and protection in cardiac catheterization laboratories. Catheterization personnel have control over the time duration of exposure, placement of technologists, shielding, location of equipment and monitoring of dose received.

A comparison of the technetium-labeled myocardial agents DiArs and DMPE to 201Tl in experimental animals

The biodistribution, kinetics, imaging characteristics and blood flow correlations of 99mTc labeled DiArs and DMPE were studied. The mice biodistribution were compared to 201Tl in mice and dogs, respectively. The myocardial kinetics of these agents were evaluated in normal and ischemic myocardium using miniaturized endocardial detectors. DiArs had a lower myocardial concentration (9.4 +/- 0.8% dose/g at 1 min), than DMPE (11.7 +/- 1.1% dose/g at 1 min) but both were considerably less than 201Tl (23-26% dose/g at 1 min). The kinetic characteristic of both technetium labeled agents suggested that redistribution into ischemic myocardium would not take place, since the clearance rate from normal and ischemic myocardium was similar for both the DiArs and DMPE . The clear visualization of the canine myocardium after i.v. injection demonstrated the superiority of DMPE over DiArs and the potential use of these agents, if proven, to behave the same in human trials.

A simplified technique for quantifying 24-h whole body retention of 99mTc-labeled methylene diphosphonate (MDP)

A simple technique for measuring 24-h whole-body retention (24-h WBR) of 99mTc-labeled methylene diphosphonate (MDP) is described. We chose a standard thyroid probe-scaler system (Picker-Magna Scanner) as our counting instrument and characterized it relative to: photon saturability; optimum counting time post administration; patient positioning; and results with prostate cancer patients with positive/negative scintigram diagnoses for bone metastases. Whole body retention values of 99mTc at 24 h were easily measured with our instrumentation. Initially whole body count rates were determined at 5-min post injection and, again at 24 h. Data accumulated prior to the 5-min time period were inaccurate due to a higher sensitivity for the activity in the early circulation. Also, initial count rates obtained from patients injected with (740 MBq) (20 mCi) 99mTc-MDP usually required a correction due to detector saturation. The data observed at 24 h, representing skeletal tracer uptake, required no such correction. Patient positioning was rigorously controlled for the two time intervals to insure constant geometry. The 24 h-WBR values measured for prostate cancer patients with positive bone scintigrams was significantly different from those patients with negative scintigrams (58.8 +/- 8.7% and 29.2 +/- 9.6% respectively). Measurement of the 24 h-WBR has great potential for following various pathologies in the clinical setting.

The effects of chemotherapy on bony metastases as measured by quantitative skeletal imaging

The effect of chemotherapy on bony metastases from adenocarcinoma of the colon was investigated by quantitative skeletal imaging over a two-month interval. The quantitative skeletal imaging results correlated with conventional blood chemistry results over this time period. While chemical assay techniques furnish an average value of lesion response, the quantitative bone scan represents a method for individual lesion analysis. This methodology has the potential to provide a better understanding of metastatic bone disease therapy.

Biodistribution of tantalum-178 A short-lived radiopharmaceutical for blood pool imaging

Abstract178Ta is a short lived radionuclide (half life=9.3 min), which results in favorable radiation exposure compared to 99mTc (half life 6 h). The energy spectrum of 178Ta consists of imageable photons in the 55–65 keV (61.2%) and 93 keV (33.7%) range but also 6% of disintegrations result in photons with energies greater than 500 keV. These high energy photons cause septal penetration in low energy collimators so that resolution is degraded. However, a medium energy collimator prevents the septal penetration of these higher energy photons. Serial blood samples obtained from dog and rabbit models indicate that 178Ta is retained in the blood pool for at least 20–30 min after intravenous injection. The 178Ta appears to be associated with the protein fraction of the plasma and not primarily with the red blood cell fraction as determined by centrifugation and column chromatography. Gated equilibrium blood pool images using 178Ta were comparable in quality to images using the 99mTc labelled red blood cell technique. Therefore, 178Ta may allow comparable equilibrium gated blood pool imaging with much more favorable radiation dosimetry. Thus, serial studies over prolonged periods of observation may be obtained.

[99mTc]pyrophosphate and [125I]phenylphosphonate behavior in the infarcted rat myocardium

Abstract The concentration of [ 125 I]phenylphosphonate ([ 125 I]φPA), was compared to that of [ 99 m Tc]pyrophosphate ([ 99 m Tc]Pyro) in a rat infarct model. Twenty-three hours after ligation of the anterior descending coronary artery, [ 125 I]φPA was given intravenously (i.v.) to 30 adult male rats. Five minutes later, 5 of these animals received [ 99 m Tc]Pyro IV and the content of 125 I and 99 m Tc was then determined at 2 h for normal (N), and infarcted (INF) heart segments. A similar investigation was completed in 5 of the animals at each of the following times post MI; 2, 3, 4, 7 and 75 days. Data were expressed as the mean (± SEM) of (% uptake/g infarct)/(% uptake/g normal) for both tracers at each study time. These data suggest that the myocardial cells which exhibit constant uptake of [ 99 m Tc]Pyro are similar to those exhibiting chronic retention of [ 125 I]φPA. The myocardial infarct to normal ratio of [ 99 m Tc]Pyro on [ 125 I]φPA showed excellent correlation ( r = 0.928) and suggests that persistent positive pyrophosphate scans are likely due to residual damaged tissue from the acute episode of necrosis, rather than the involvement of newly injured tissue.

Patient and Occupational Dosimetry

With the introduction of dual-modality positron emission and transmission computed tomography (PET/CT) systems, concurrent acquisition and subsequent generation of coregistered functional (PET) and anatomic (CT) images have become the preferred diagnostic method.1–4 This capability has caused concern about increased patient radiation doses and occupational exposures to healthcare personnel.5–8 To address this concern, we need to determine the patient’s optimum administered radiopharmaceutical dosage and the appropriate CT scanning parameters as well as to instruct personnel in radiation-exposure-reduction techniques. The CT component can be used to correct for tissue attenuation, which is otherwise accomplished with an external radionuclide source, or to generate diagnostically suitable CT images. In either case, there should be an attempt to minimize the radiation dose while maintaining the diagnostic efficacy of the scan.

Dual tracer resorption and apposition in a rat fracture model.

The simultaneous measurement of tracer resorption and apposition in a rat fracture model was accomplished with 99mTc labeled methylene diphosphonate (99mTc-MDP) and 125I labeled phenylphosphonic acid (125I-phi PA), respectively. Loss of 125I-phi PA from the fracture site showed a biexponential release pattern; I = 31% (t1/2b = 2.0 d) and II = 69% (t1/2b = 55.4 d). 99mTc MDP temporal apposition at the fracture site followed the law of allometric growth (y = bxk) with k = 7.75, 10 days post injury. The 125I-phi PA loss differed significantly (P less than 0.001) when compared to normal bone which exhibits a monoexponential release with a t1/2b = 962 days. In the rat tibia fracture model investigated, bone apposition significantly (P less than 0.001) dominates over bone resorption as a function of time. This overwhelming difference partially accounts for the healing process. The apposition-resorption comparison may be a useful index for following the course of skeletal pathology for a variety of model systems.

The 4h/24h 99mTc-MDP whole body retention: A new index of bone pathology

A simple technique for determining the whole body retention of 99mTc labeled methylene diphosphonate (MDP) at 4-h and 24-h was applied to 28 adult patients (22 prostate cancer, 6 osteoporosis). Following administration of 20 mCi (740 MBq) 99mTc-MDP, a qualitative scintigram was performed and whole body retention was recorded at 4 and 24 h. The prostate cancer patients all had positive bone scintigrams, and of this group, 7 were in relapse and 15 in remission on chemotherapy. The osteoporotic groups whole body retention values were determined prior to the initiation of drug therapy. Mean percent whole body retention values were significantly greater at 4 and 24 h for the cancer patients in relapse relative to both the prostate cancer patients in remission and the osteoporotics: 4-h%/24-h%; equals 74.3/60.2, 57.5/33.5, and 48.0/30.3, respectively. The whole body retention values of the latter two groups, however, were only significantly different at 4-h. An additional index of skeletal pathology was developed by combining the 4-h/24-h values to calculate the biological half time (t1/2b) for this time period using a single exponential model. Again the cancer patients in relapse exhibited a significantly longer half time relative to those in remission and the osteoporotics (70.4 vs 25.7 h and 29.2 h, respectively). The combination of 4 and 24-h whole body retention values with the associated t1/2b has potential for following and classifying patients during the course of their skeletal disease. These values have been shown to be especially valuable with cancer patients with metastatic disease.