We retrospectively evaluated our single-center clinical experience with (90)Y-ibritumomab tiuxetan and (131)I-tositumomab for therapy of refractory non-Hodgkin's lymphoma (NHL). We evaluated the ...hypothesis that the patient-specific dosing regimen used with (131)I-tositumomab results in less bone marrow toxicity than does the weight-based dosing regimen used with (90)Y-ibritumomab tiuxetan.
Thirty-eight patients (25 male and 13 female; median age, 64 y) received radioimmunotherapy for NHL (20 received (90)Y-ibritumomab tiuxetan; 18 received (131)I-tositumomab). Patient and disease characteristics were evaluated to determine whether any were prognostic indicators of short- or long-term clinical response. The 12-wk response rate and clinical and hematologic toxicities attributable to each therapy were assessed. The response rate at 12 wk was correlated with long-term overall survival.
Twenty-six patients received full-radiation-dose radioimmunotherapy and 12 received attenuated doses because of hematologic concerns. The 12-wk overall response rate for all patients was 47%, and the complete response rate was 13%. The 12-wk overall response rate did not significantly differ between the (90)Y-ibritumomab tiuxetan and (131)I-tositumomab groups. Responses at 12 wk were more frequent in patients with normal levels of serum lactate dehydrogenase, no bone marrow involvement, and International Prognostic Index scores of no more than 2 (P < or = 0.04). Grade 3 or 4 thrombocytopenia occurred in 57% and 56% of patients treated with (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, respectively. Grade 3 or 4 neutropenia was observed in 57% and 50%, respectively. The time to the absolute neutrophil count nadir was shorter for the (90)Y-ibritumomab tiuxetan group than for the (131)I-tositumomab group (36 +/- 9 vs. 46 +/- 14 d, P = 0.01). The mean percentage decline in platelet count after radioimmunotherapy was greater in the (90)Y-ibritumomab tiuxetan group than in the (131)I-tositumomab group (79% +/- 17% vs. 63% +/- 28%, P = 0.04). Overall survival was longer in responders than in nonresponders 12 wk after therapy (P < or = 0.05).
Both (90)Y-ibritumomab tiuxetan and (131)I-tositumomab were well tolerated. We observed response rates at the lower range of those reported in the literature, possibly because of referral bias, dose attenuation, and reasonably liberal acceptance criteria for a patient to receive therapy. Initial response assessments 12 wk after radioimmunotherapy predict longer-term response. (131)I-tositumomab caused significantly less severe declines in platelet counts than did (90)Y-ibritumomab tiuxetan and may be a more appropriate choice for patients with limited bone marrow reserve, but large, randomized, prospective trials are needed to better compare the performance of these 2 treatments.
Total serum thyroxine (T4), triiodothyronine (T3), T3 resin uptake (T3U), thyrotrophin (TSH), and reverse T3 (rT3) were measured in 209 healthy adults 20--89 yr old. Mean T4 values for men were ...stable throughout life, but in females under age 60, T4 values were significantly higher than in older women. Values for T3U in males were significantly higher than in females throughout all decades, although females had a significant increase in T3U after age 60. TSH values increased significantly in females over age 60. Throughout all decades, males had stable TSH levels that were slightly higher than the female results before age 60 and lower thereafter. Mean serum T3 declined similarly for both sexes with increasing age, although not to the extent previously reported. Men had significantly higher mean rT3 values over all decades than females, although female rT3 levels decreased after age 50 whereas males maintained stable values. The physiologic reasons for these findings may be due to sex-related changes in binding proteins and alterations in metabolic clearance rates, production, and degradation of these hormones with increasing age.
In 16 patients we have carried out simultaneous plasma-volume measurements with human serum albumins tagged with Tc-99m (Tc-99m HSA) and I-131 (I-131 HSA). The correlation coefficient was 0.987. ...Tc-99m HSA, prepared from kits that predictably yield high labeling efficiency (and thereby negligible amounts of TCO4-), is clearly a superior agent for repeat plasma volume determinations, because of its shorter half-life and the reduced radiation dose to the subject.
A quantitative method for external detection of mesenteric arteriovenous shunts was developed. 99mTc-Human Serum Albumin Microspheres (15--30 microns) were injected into the superior mesenteric ...artery of dogs through an angiographic catheter, followed by external scintillation counting of the liver activity, which represented the shunted spheres. Thereafter, 99mTc-sulfur colloid was injected identically and the liver activity counted again. The liver net count after sulfur colloid represented a 100% shunt, when a correction factor for the actual liver uptake was applied. The a shunt rate was calculated. Eleven animal studies were performed and shunt rates similar to previous in vitro determinations were obtained. This method is suitable for clinical investigation and can conveniently be applied to mesenteric arteriography.
We report a case of massive cerebrospinal fluid (CSF) leakage where the tracer injected intra-thecally for radionuclide cisternography was later visualized in the bowel as well as the nasopharynx. We ...discuss the potential implications of this finding in patients with CSF leaks. A brief review of the diagnosis of CSF leaks is included.
Study of the effects of various diseases and therapeutic manipulation of pulmonary vascular resistance on the right ventricle has been restricted by methodologic limitations. The radioactive gas in ...solution, krypton-81m was used to study the right ventricle and the technique was compared with a technetium-99m method. In 22 subjects, first-pass krypton-81m right ventricular ejection fraction, acquired both in list mode and electrocardiogram-gated frame mode, correlated well (r = 0.81 and 0.86, respectively, p less than 0.01) with that determined by technetium-99m first-pass studies over a broad range of ventricular function. The reproducibility of the technique was excellent (r = 0.84 and 0.95 for each acquisition mode, respectively). Krypton-81m first-pass studies provide accurate and reproducible estimates of right ventricular function. Use of krypton allows multiple measurements, with or without perturbations, over a short period of time.
A fully automated program developed by us for measurement of left ventricular ejection fraction from equilibrium gated blood pool studies was evaluated in 130 additional patients. Both 6-min (130 ...studies) and 2-min (142 studies in 31 patients) gated blood pool studies were acquired and processed. The program successfully generated ejection fractions in 86% of the studies. These automatically generated ejection fractions were compared with ejection fractions derived from manually drawn regions of interest. When studies were acquired for 6-min with the patient at rest, the correlation between automated and manual ejection fractions was 0.92. When studies were acquired for 2-min, both at rest and during bicycle exercise, the correlation was 0.81. In 25 studies from patients who also underwent contrast ventriculography, the program successfully generated regions of interest in 22 (88%). The correlation between the ejection fraction determined by contrast ventriculography and the automatically generated radionuclide ejection fraction was 0.79.
Purpose: We prospectively evaluated the feasibility of SPECT-CT/planar organ dosimetry-based radiation dose escalation radioimmunotherapy in patients with recurrent non-Hodgkin’s lymphoma using the ...theranostic pair of 111In and 90Y anti-CD20 ibritumomab tiuxetan (Zevalin®) at myeloablative radiation-absorbed doses with autologous stem cell support. We also assessed acute non-hematopoietic toxicity and early tumor response in this two-center outpatient study. Methods: 24 patients with CD20-positive relapsed or refractory rituximab-sensitive, low-grade, mantle cell, or diffuse large-cell NHL, with normal organ function, platelet counts > 75,000/mm3, and <35% tumor involvement in the marrow were treated with Rituximab (375 mg/m2) weekly for 4 consecutive weeks, then one dose of cyclophosphamide 2.5 g/m2 with filgrastim 10 mcg/kg/day until stem cell collection. Of these, 18 patients with successful stem cell collection (at least 2 × 106 CD34 cells/kg) proceeded to RIT. A dosimetric administration of 111In ibritumomab tiuxetan (185 MBq) followed by five sequential quantitative planar and one SPECT/CT scan was used to determine predicted organ radiation-absorbed dose. Two weeks later, 90Y ibritumomab tiuxetan was administered in an outpatient setting at a cohort- and patient-specific predicted organ radiation-absorbed dose guided by a Continuous Response Assessment (CRM) methodology with the following cohorts for dose escalation: 14.8 MBq/kg, and targeted 18, 24, 28, and 30.5 Gy to the liver. Autologous stem cell infusion occurred when the estimated marrow radiation-absorbed dose rate was predicted to be <1 cGy/h. Feasibility, short-term toxicities, and tumor response were assessed. Results: Patient-specific hybrid SPECT/CT + planar organ dosimetry was feasible in all 18 cases and used to determine the patient-specific therapeutic dose and guide dose escalation (26.8 ± 7.3 MBq/kg (mean), 26.3 MBq/kg (median) of 90Y (range: 12.1–41.4 MBq/kg)) of ibritumomab tiuxetan that was required to deliver 10 Gy to the liver. Infused stem cells engrafted rapidly. The most common treatment-related toxicities were hematological and were reversible following stem cell infusion. No significant hepatotoxicity was seen. One patient died from probable treatment-related causes—pneumonia at day 27 post-transplant. One patient at dose level 18 Gy developed myelodysplastic syndrome (MDS), 4 patients required admission post-90Y RIT for febrile neutropenia, 16/18 patients receiving 90Y ibritumomab tiuxetan (89%) responded to the therapy, with 13 CR (72%) and 3/18 PR (17%), at 60 days post-treatment. Two patients had progressive disease at sixty days. One patient was lost to follow-up. Median time to progression was estimated to be at least 13 months. MTD to the liver is greater than 28 Gy, but the MTD was not reached as the study was terminated due to unexpected discontinuation of availability of the therapeutic agent. Conclusions: Patient-specific outpatient 90Y ibritumomab tiuxetan RIT with myeloablative doses of RIT up to a targeted 30.5 Gy to the liver is feasible, guided by prospective SPECT/CT + planar imaging with the theranostic pair of 111In and 90Y anti-CD20, with outpatient autologous stem cell transplant support. Administered activity over 5 times the standard FDA-approved activity was well-tolerated. The non-hematopoietic MTD in this study exceeds 28 Gy to the liver. Initial tumor responses were common at all dose levels. This study supports the feasibility of organ dosimetry-driven patient-specific dose escalation in the treatment of NHL with stem cell transplant and provides additional information on the radiation tolerance of the normal liver to radiopharmaceutical therapy.
The lungs are the most frequent sites of distant metastasis in differentiated thyroid carcinoma. Radioiodine treatment planning for these patients is usually performed following the Benua-Leeper ...method, which constrains the administered activity to 2.96 GBq (80 mCi) whole-body retention at 48 h after administration to prevent lung toxicity in the presence of iodine-avid lung metastases. This limit was derived from clinical experience, and a dosimetric analysis of lung and tumor absorbed dose would be useful to understand the implications of this limit on toxicity and tumor control. Because of highly nonuniform lung density and composition as well as the nonuniform activity distribution when the lungs contain tumor nodules, Monte Carlo dosimetry is required to estimate tumor and normal lung absorbed dose. Reassessment of this toxicity limit is also appropriate in light of the contemporary use of recombinant thyrotropin (thyroid-stimulating hormone) (rTSH) to prepare patients for radioiodine therapy. In this work we demonstrated the use of MCNP, a Monte Carlo electron and photon transport code, in a 3-dimensional (3D) imaging-based absorbed dose calculation for tumor and normal lungs.
A pediatric thyroid cancer patient with diffuse lung metastases was administered 37 MBq of (131)I after preparation with rTSH. SPECT/CT scans were performed over the chest at 27, 74, and 147 h after tracer administration. The time-activity curve for (131)I in the lungs was derived from the whole-body planar imaging and compared with that obtained from the quantitative SPECT methods. Reconstructed and coregistered SPECT/CT images were converted into 3D density and activity probability maps suitable for MCNP4b input. Absorbed dose maps were calculated using electron and photon transport in MCNP4b. Administered activity was estimated on the basis of the maximum tolerated dose (MTD) of 27.25 Gy to the normal lungs. Computational efficiency of the MCNP4b code was studied with a simple segmentation approach. In addition, the Benua-Leeper method was used to estimate the recommended administered activity. The standard dosing plan was modified to account for the weight of this pediatric patient, where the 2.96-GBq (80 mCi) whole-body retention was scaled to 2.44 GBq (66 mCi) to give the same dose rate of 43.6 rad/h in the lungs at 48 h.
Using the MCNP4b code, both the spatial dose distribution and a dose-volume histogram were obtained for the lungs. An administered activity of 1.72 GBq (46.4 mCi) delivered the putative MTD of 27.25 Gy to the lungs with a tumor absorbed dose of 63.7 Gy. Directly applying the Benua-Leeper method, an administered activity of 3.89 GBq (105.0 mCi) was obtained, resulting in tumor and lung absorbed doses of 144.2 and 61.6 Gy, respectively, when the MCNP-based dosimetry was applied. The voxel-by-voxel calculation time of 4,642.3 h for photon transport was reduced to 16.8 h when the activity maps were segmented into 20 regions.
MCNP4b-based, patient-specific 3D dosimetry is feasible and important in the dosimetry of thyroid cancer patients with avid lung metastases that exhibit prolonged retention in the lungs.
PDF
