Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer.

Samarium-153 emits medium-energy beta particles and an imageable gamma photon with a physical half-life of 46.3 hr. When chelated to ethylenediaminetetramethylenephosphonic acid (EDTMP), it is remarkably stable in vitro and in vivo. In this study, we administered escalating amounts of 153Sm-EDTMP, from 0.1 to 1.0 mCi/kg (3.7-37 MBq/kg), to 22 patients with painful metastatic bone cancer. A complete concordance was found when the scintigrams of 153Sm-EDTMP were compared qualitatively to 99mTc-HDP bone images. Moreover, the skeletal uptake of the 153Sm-EDTMP related to the number of metastatic sites (r = 0.65; p = 0.001) showed an inverse proportion to the plasma radioactivity at 30 min following injection (r = -0.79; p = 0.0001) and was unaffected by the administered (mCi/kg), (r = 0.33; p = 0.13). Myelotoxicity was observed in 10 of the 29 treatment courses and leukopenia occurred in two. Thrombocytopenia occurred in patients who had low pretreatment platelet counts, albeit within the normal range (p = 0.001), most suffered from prostate cancer (p = 0.007) and retained a higher percentage of the 153Sm-EDTMP in their skeleton (p = 0.057). In four patients an exacerbation of the pre-existing pain ("flare reaction") was recorded. Pain palliation occurred in 65% of the treated patients (mean: 3.8 mo, range: 1-11 mo). Retreatment in first time responder patients was quite effective. Our preliminary results indicate that 153Sm-EDTMP is a promising radiotherapeutic agent for palliative treatment of metastatic bone cancer pain, and further study is necessary to ascertain its optimal dose, efficacy and toxicity.

Single photon scatter compensation by photopeak energy distribution analysis.

Scattered photons degrade nuclear medicine image contrast and resolution, and preclude simple attenuation corrections. Current scatter correction methods utilize detected events with energies below pulse height analyzer (PHA) window levels, making attenuation corrections source position dependent. This new scatter rejection technique analyzes only the photon signals occurring within the range of standard PHA windows. In real time, at each image location the PHA window energy distribution is analyzed, a scatter fraction determined, and a scatter corrected number of events are output. The method can be adapted to any imaging system which produces event location and energy signals. Attenuation corrections (u=0.15 cm(-1), 140 keV) are within 6% for 2-10 cm depths.

Aneurysmectomy prognosticators by equilibrium multi-gated cardiac blood pool scintigraphy.

Non-invasive assessment of left ventricular aneurysm (LVA) resection prognosticators was obtained in 13 multigated cardiac blood pool scintigrams by applying Fourier analysis to identify regions of interest. Results were compared to contrast ventriculograms performed at recent cardiac catheterization. Excellent correlation of the contractile section ejection fraction (CSEF) was found between the two techniques, r = .92 (P less than or equal to .0001). The CSEF correlated inversely with the left ventricular end diastolic pressure (LVEDP), r = .83 (P less than or equal to .0004), implying that LVEDP is not an independent prognosticator. The relative LVA size expressed as a fraction of the left ventricle in end diastole (LVASF) correlated less strongly with LVASF derived from contrast ventriculography, r = .67 (P = .012). This was probably due to additive inherent errors in contrast ventriculography geometric assumptions. Paradoxical stroke steal fraction (PSSF) defined as the reverse stroke lost in the LVA divided by the left ventricular forward stroke, was calculated from subtraction images. We propose a resectability score utilizing the product of the scintigraphically derived CSEF X LVASF X PSSF X 1,000 to obtain non-invasive pre-operative prognostication of LVA resection and post-operative evaluation.

Total and split renal function in patients with renovascular hypertension: effects of angiotensin-converting enzyme inhibition.

Thirteen subjects with documented renovascular hypertension receiving chronic (greater than 1 month) therapy with an angiotensin-converting enzyme inhibitor (enalapril or captopril) underwent total and split renal function studies. Total glomerular filtration rate as assessed by inulin clearance was similar to that determined by radionuclide technique. Total effective renal plasma flow as assessed by p-aminohippurate clearance was lower than that determined by radionuclide technique. The glomerular filtration rate and effective renal plasma flow assessed by radionuclide technique of the stenotic kidney was comparatively lower than that of the non-stenotic kidney. No subject demonstrated complete loss of filtration or perfusion of the stenotic kidney. Five of six patients studied prospectively for 2 years have demonstrated stability of total renal function; the sixth patient, having a functional solitary stenotic kidney, has demonstrated stability of function following an initial abrupt decline in glomerular filtration rate and effective renal plasma flow. These results suggest that chronic angiotensin-converting enzyme inhibition therapy is not generally associated with near total absence of filtration of the stenotic kidney as has been suggested previously. Angiotensin-converting enzyme inhibitors may be safely and effectively utilized in the treatment of renovascular hypertension.

Radiation dose calculations in persons receiving injection of samarium-153 EDTMP.

Samarium-153 EDTMP has been proposed as a radionuclide therapeutic agent to treat malignant bone tissue disorders. Data obtained from laboratory rats has been used to calculate the radiation dose for humans following the administration of [153Sm]EDTMP. The data reveals that the highest doses are present in the skeleton and the urinary bladder wall (bladder dose varies with frequency of voiding). Skeletal activity was used to estimate the bone marrow dose from the [153Sm]EDTMP beta radiation. Although this estimate indicates high marrow irradiation it is only an approximation since the beta radiation from inhomogeneously deposited bone activity surrounding the marrow produces variable radiation dose distributions.

Quantitative SPECT imaging for diagnosis and dosimetry in radionuclide therapy.

Effective therapeutic treatment with in vivo administered radioactivity depends on the localization of appropriate concentrations in tissues to be treated. Accurate assessment of both diagnostic and therapeutic concentrations of radiopharmaceuticals is the goal of quantitative SPECT imaging. The technology of SPECT imaging has significantly improved over the past 5 years, and routine quantitation for SPECT users may not be far away. The four operational steps by quantitative SPECT imaging are described, along with technical factors that require further development before it can be used routinely.

Clinical problems associated with dosimetry of 125-iodine for cancer of the prostate.

Dosimetry and clinical data for iodine-125 prostatic seed implants in 63 patients were retrospectively studied to evaluate the methods of calculating the effective implant activity. Our protocol called for 10 000 cGy to the periphery of the prostate from 125I and 4 000 cGy to the whole pelvis in 20 fractions from supervoltage. Most procedures used seed strengths of 20.35 to 21.09 MBq (0.55-0.57 mCi). The average number of seeds lost per patient was 2.1 without prior transurethral prostatic resection (TURP), and 5.6 with prior TURP. Specific precautions are recommended to minimize seed loss. In a 3 cm diameter gland with uniform seed distribution, the periphery received 10 000 cGy, while the central 2 cm diameter core received 20 000 cGy. Near the periphery there was a rapid decrease in dose averaging 1 390 cGy per millimeter radially. Because of this rapid fall-off, it may be misleading to specify the dose in cGy only. It is recommended that the total 125I activity per implant also be specified in the same way as mghr-of-radium-equivalent for cancer of the cervix. Recommended total activities needed for implantation in various prostate gland sizes are given.

Gamma camera MTFs from edge response function measurements.

An experimental procedure using edge response functions (ERF) has been devised to rapidly provide modulation transfer function (MTF) values for gamma camera imaging. Both camera intrinsic and system MTFs are generated. This procedure uses a simple test tool to generate the ERF which is then processed by a computer program using a cubic splines differentiation technique and a discrete Fourier transform algorithm to produce the MTF values. An analytic test of the computer algorithms as well as an experimental test using collimator data from the Bureau of Radiological Health is presented to confirm the accuracy of the procedure.

Cardiac phase: amplitude analysis using macro programming.

The analysis of EKG gated radionuclide cardiac imaging data with Fourier amplitude and phase images is becoming a valuable clinical technique, demonstrating location, size, and severity of regional ventricular abnormalities. Not all commercially available nuclear medicine computer systems offer software for phase and amplitude analysis; however, many systems do have the capability of linear image arithmetic using simple macro commands which can easily by sequenced into stored macro-strings or programs. Using simple but accurate series approximations for the Fourier operations, macro programs have been written for a Digital Equipment Corporation Gamma-11 system to obtain phase and amplitude images from routine gated cardiac studies. In addition, dynamic cine-mode presentation of the onset of mechanical systole is generated from the phase data, using only a second set of macro programs. This approach is easily adapted to different data acquisition protocols, and can be used on any system with macro commands for image arithmetic.

Doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction: a sign of poor long-term prognosis.

Thirty survivors of acute myocardial infarction with 3+ or 4+ positive technetium-99m pyrophosphate myocardial scintigrams were followed up for 28 +/- 3.1 months (mean +/- standard deviation). Three patient groups were identified from the pattern of radioactive uptake in the scintigram: Group I, 16 patients with focal uptake (anterior in 7, lateral in 2, posterior in 3 and inferior in 4); Group II, 6 patients with anterior myocardial infarction and a doughnut pattern of uptake; Group III, 8 patients with nontransmural myocardial infarction and a diffuse pattern of uptake. Late complications developed in all patients with the doughnut pattern of uptake compared with 43 percent of patients with the focal pattern and 12 percent of patients with the diffuse pattern. After discharge from the hospital, five of six patients with a doughnut pattern of uptake died (mean survival time 9.8 months after the initial myocardial infarction). This mortality rate (83 percent) was significantly greater than that of patients with a focal (mortality rate 6 percent) or diffuse (no mortality) pattern of uptake. The doughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction appears to identify a subgroup of patients with a very poor long-term prognosis.

Limited clinical diagnostic specificity of technetium-99m stannous pyrophosphate myocardial imaging in acute myocardial infarction.

To test the sensitivity and specificity of technetium-99m stannous pyrophosphate myocardial imaging in the diagnosis of acute myocardial infarction, myocardial scintigrams were performed in 115 patients. Positive scintigrams were found in all 48 patients with acute myocardial infarction; uptake was localized in 29 patients with transmural infarction and diffuse in 2 patients with transmural infarction and in the remaining 17 patients with subendocardial myocardial infarction. Positive scintigrams were also found in 31 of 67 patients without clinical evidence of acute myocardial infarction. Diffusely positive scintigrams were found in 3 of 3 patients with unstable angina pectoris, 7 of 30 patients with stable angina pectoris, 4 of 13 patients who had undergone aortocoronary bypass surgery, 4 of 4 patients with congestive cardiomyopathy and 1 patient studied 1 day after direct current cardioversion. Localized uptake of 99mTc-pyrophosphate was found in 9 of 10 patients with left ventricular aneurysm and in 3 of 13 patients after aortocoronary bypass surgery. All four patients with atypical chest pain and two patients with pericarditis had normal scintigrams. Our data confirm the previously reported sensitivity of 99mTc-pyrophosphate imaging in detection of acute myocardial infarction but indicate that positive scintigrams are not specific for this entity.