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Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for all patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question.

Background: A novel prognostic staging classification encompassing all forms of thyroid carcinoma was created for the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) Registry, with the goal of prospective validation and comparison with other available staging classifications., Methods: Patient information was recorded prospectively from 14 institutions. Clinicopathologic staging was based on patient age at diagnosis, tumor histology, tumor size, intrathyroidal multifocality, extraglandular invasion, metastases, and tumor differentiation., Results: Between 1987 and 1995, 1607 patients were registered. Approximately 43% of patients were classified as NTCTCS Stage I, 24% Stage II, 24% Stage III, and 9% Stage IV. Patients with follicular carcinoma were more likely to have "high risk" Stage III or IV disease than those with papillary carcinoma. Of 1562 patients for whom censored follow-up was available (median follow-up, 40 months), 78 died of thyroid carcinoma or complications of its treatment. Five-year product-limit patient disease specific survival was 99.8% for Stage I, 100% for Stage II, 91.9% for Stage III, and 48.9% for Stage IV (P < 0.0001). The frequency of remaining disease free also declined significantly with increasing stage (94.3% for Stage I, 93.1%for Stage II, 77.8% for Stage III, and 24.6% for Stage IV). The same patients also were staged applying six previously published classifications as appropriate for their tumor type. The predictive value of the NTCTCS Registry staging classification consistently was among the highest for disease specific mortality and for remaining disease free, regardless of the tumor type., Conclusions: The NTCTCS Registry staging classification provides a prospectively validated scheme for predicting short term prognosis for patients with thyroid carcinoma.

Unlabelled: Rhenium-188 (tin) hydroxyethylidine diphosphonate [188Re(Sn)HEDP] is a new radiopharmaceutical that localizes in skeletal metastases and emits beta particles that may be therapeutically beneficial., Methods: It was evaluated by in vitro and in vivo testing in the laboratory, in animals and in humans using 188Re from a variety of sources. It may be produced by a desk-top method developed previously for 186Re(Sn)HEDP using 188Re produced through neutron irradiation of either enriched 187Re or naturally occurring rhenium targets or the use of a 188W/188Re generator., Results: So long as the mass of rhenium in the 188Re-perrhenate to be processed into 188Re(Sn)HEDP is at least 100 microg, satisfactory radiochemical yields and purity may be obtained by all methods. The 188Re(Sn)HEDP has biodistribution and radiation dosimetry characteristics that are similar to those noted previously for 186Re(Sn)HEDP and appears to result in similar benefits and toxicities in patients with skeletal metastases. External radiation exposure monitoring indicates that, only 4 hr after a therapeutic administration of 1110 MBq (30 mCi) of 188Re(Sn)HEDP, average exposure rates at 1 meter from the patient would be only 0.5 mR/hr., Conclusion: Same-day, on-demand, outpatient therapy of disseminated skeletal metastases appears to be feasible with 188Re(Sn)HEDP.

Early diagnosis of osteomyelitis continues to be a clinical problem. Multiple imaging modalities are being used for the diagnosis of osteomyelitis, but none of them is ideal for all cases. The choice of modality depends on several factors based on an understanding of the pathophysiologic aspects of different forms of osteomyelitis. After a brief introduction outlining some basic principles regarding the diagnosis of osteomyelitis, pathophysiologic aspects are reviewed. Advantages and disadvantages of each imaging modality and their applications in different forms of osteomyelitis are discussed. The use of different imaging modalities in the diagnosis of special forms of osteomyelitis, including chronic, diabetic foot, and vertebral osteomyelitis, and osteomyelitis associated with orthopedic appliances and sickle cell disease is reviewed. Taking into account the site of suspected osteomyelitis and the presence or absence of underlying pathologic changes and their nature, an algorithm summarizing the use of various imaging modalities in the diagnosis of osteomyelitis is presented.

Background: Trans (N,N'-ethylene bis(acetylacetoneimine)) bis(tris(3-methoxy-1-propyl) phosphine) 99mTc(III) (99mTc-Q3) has been developed for myocardial perfusion imaging. Biokinetic studies and dosimetry analysis have been completed for six healthy volunteers., Methods and Results: The same-day two-injection protocol involved (1) an average rest injection of 241 MBq of 99mTc-Q3 followed by myocardial single-photon emission computed tomography (SPECT) at 15.0 minutes and a whole body (WB) scan at 1.5 hours; and (2) an average stress injection during treadmill exercise of 744 MBq of 99mTc-Q3 at 2.4 hours (postrest injection) followed by myocardial SPECT and additional WB scans at 1.5, 3.5, 6.5, and 21 hours poststress injection. Total urine was collected over 24 hours. Absolute organ activities were determined by conjugate counting methods. The two-injection data were simplified to a one-injection equivalent data set to facilitate dosimetry analysis. Decay corrected average percentage uptake values, plus or minus one standard deviation, for the myocardium were 1.4% +/- 0.2% at approximately 1.5 hours for both the postrest and poststress injections. The average biologic half-time for the myocardium was 26.4 hours. The highest organ uptake values included the gallbladder with 5.5% +/- 1.9% and the liver with 4.1% +/- 1.0% at the 1.5 hours poststress scan time. The sum of all gastrointestinal (GI) tract components was 18.8% +/- 9.4% at approximately 6.5 hours poststress injection (before any fecal elimination). The total 24 hour urine clearance was 17.1% +/- 2.4%. The gallbladder wall and upper large intestine wall received the highest doses at 0.024 and 0.023 mGy/MBq, respectively., Conclusion: The effective dose equivalent is estimated to be 0.01 mSv/MBq, which for an administration of 1110 MBq (30 mCi) is less than half that of a standard imaging protocol using 111 MBq (3 mCi) of 201Tl, and comparable to the published estimates for 99mTc-labeled sestamibi and 99mTc-labeled tetrofosmin (also normalized to 1110 MBq of administered activity). The 99mTc-Q3 exhibits myocardium uptake similar to that for these other two 99mTc agents.

99mTc pentavalent dimercaptosuccinic acid [99mTc (V) DMSA], a useful agent for imaging thyroid medullary carcinoma and other tumors, can be reliably prepared by addition of NaHCO3 and then Na99mTcO4 to a commercial kit for 99mTc trivalent DMSA [99mTc (III) DMSA], followed by bubbling oxygen through the solution for 10 min. 99mTc (V) DMSA made by this method is radiochemically pure and stable for 24 h, and it gives a rat biodistribution similar to that of the agent made by previous methods. Clinical biodistribution and radiation dosimetry studies are planned.

Unlabelled: A Monte Carlo model has been developed for simulation of dose delivery to skeletal metastases by the bone surface-seeking radiopharmaceutical 186Re (Sn)-HEDP., Methods: The model simulates: (1) the heterogeneous small scale geometry of the soft tissue/bone-spicule structure in the lesions as determined by histomorphometric measurements of histologic specimens, (2) the small scale spatial distribution of the radiopharmaceutical on the lesion bone spicule surface as determined by autoradiography, and (3) the 186Re beta and conversion electron decay spectrum and the associated charged particle transport within the modeled geometries. The results are compared with the commonly employed uniform lesion model, which assumes: (1) homogeneous lesion morphology, (2) uniform distribution of radioactivity within the lesion, and (3) complete energy deposition by charged particles within the lesion due to decay of this activity. Gamma and x-ray photons from the 186Re spectrum were assumed to escape from the lesion volume in both models., Results: Results show a significant dependence on the bone volume fraction and hence on the histology of the lesion (lytic, blastic or mixed). The uniform lesion model calculations underestimate the radiation dose to blastic lesions by as much as a factor of 1.8. However, for lytic lesions with low bone volume fractions, both models provide similar dose values., Conclusions: These new model calculations provide a mechanism for optimizing treatment planning and dose response evaluations of therapeutic bone-seeking radiopharmaceuticals.

Thirty-one adult patients with clinical findings suggestive of pheochromocytoma were studied with I-123 MIBG. All patients had images obtained at 24 and 48 hours. Five patients had abnormal uptake proved to be because of I-123 MIBG avid tumors. The remaining 26 patients had no proven tumors and showed physiologic uptake in various organs. The 24-hour images were of high quality. In all cases, the 48-hour images contributed no significant additional information. Only in 1 patient did the 48-hour image add some certainty. Physiologic uptake was seen in the salivary glands, liver, G.I. tract, and urinary bladder in all patients (100%). Uptake was also observed in the lung and heart (90%), normal adrenal glands (32%), thyroid (29%), spleen (23%) uterus (13%), and neck muscles (6%). The authors' experience indicates that I-123 MIBG gives superior images compared to the previously used I-131 MIBG, that the optimum imaging time for adults is 18-24 hours, and that normal distribution patterns including uterine and neck muscle uptake should be familiar to physicians interpreting the studies.

Introduction: The treatment of primary thyroid cancer requires protracted follow-up because of to the possibility of the development of recurrent metastases many years after the initial diagnosis. Often such follow-up involves imaging at regular intervals with diagnostic I-131 studies. However, not all thyroid cancer concentrates I-131. The purpose of this article is to review the efficacy of alternative diagnostic imaging modalities for follow-up of thyroid carcinomas that do not concentrate radioiodine., Materials and Methods: These procedures include the use of nuclear medicine imaging with thallium-201 (TI-201), Tc-99m-sestamibi, Tc-99m pentavalent dimercaptosuccinic acid (DMSA), radiolabeled anti-carcinoembryonic antigen antibodies, and radioiodinated-131 meta-iodobenzyl guanidine, as well as computerized x-ray tomography, magnetic resonance imaging (MRI), and ultrasound (US)., Results and Conclusion: Thallium-201, MRI, and pentavalent DMSA provide adequate sensitivity for follow-up of selected patients with suspected recurrent noniodine concentrating thyroid carcinoma.

Bone marrow depression following 131I therapy for metastatic thyroid cancer can occur in up to one-quarter of all patients so treated. An analysis was made of the 131I whole body (WB) retention and its relationship to activity in blood for 46 patients (45 adult, 1 adolescent in 49 total studies) to define the accuracy of utilizing WB external counting data as a predictor of blood dose in comparison to the more classical method which requires data from sequential blood samples. The mean percentage differences between blood dose estimates based on external WB counting and those calculated by the classical method lie within +/- 10%. The WB methodology provides a useful first-order approximation for hematopoietic dose estimates in adult patients undergoing 131I therapy for thyroid cancer.

Duodenogastric reflux (DGR) as seen on hepatobiliary scintigraphy has been reported as a useful secondary sign for the diagnosis of acute cholecystitis. We evaluated the association of reflux with cases of acute cholecystitis as compared to those with chronic cholecystitis or other conditions. Thirty-six of 198 patients referred for hepatobiliary imaging showed DGR (18%). Among 26 patients with acute cholecystitis, 6 (23%) had DGR as compared to 9/40 (23%) cases with chronic cholecystitis, 3/12 cases with acute pancreatitis, 4/13 cases with previous cholecystectomy, and 3/8 cases with duodenal ulcer. No statistically significant differences were found between the prevalence of DGR in cases with acute cholecystitis and those with chronic cholecystitis or other nonacute cholecystitis diagnostic categories. Although acute cholecystitis is a condition frequently associated with DGR, such reflux is a nonspecific finding and should not be considered as a secondary sign of acute cholecystitis when interpreting hepatobiliary scans.

For almost five decades, 131I treatment of thyroid cancer has been based empirically on administered activity rather than on actual radiation doses delivered. In 1983, we defined radiation dose thresholds for successful treatment. This report is concerned with the subsequent validation of those thresholds in 85 patients. The successful ablation of thyroid remnants occurred after a single initial 131I administration in 84% of inpatients and in 79% of outpatients when treatment was standardized to a radiation dose of at least 30,000 cGy (rad). Administered activities low enough to permit outpatient therapy could be used in 47% of the patients. Lymph node metastases were treated successfully in 74% of patients with a single administration of 131I calculated to deliver at least 8,500 cGy (rad). For athyrotic patients with nodal metastases only, success was achieved in 86% of patients at tumor doses of at least 14,000 cGy (rad). These success rates are equal to or better than those reported with empiric methods of 131I administration. The individualized treatment planning selectively allocates hospitalization and higher exposures to 131I to those patients who require them.

Single intravenous injections of 30 to 35 mCi (1,110 to 1,295 MBq) of Re-186(Sn)HEDP previously have been shown to result in palliation of painful skeletal metastases from prostate cancer. There are no reports of patients receiving repetitive Re-186(Sn)HEDP therapy. We have followed two such patients who received multiple (five to seven) injections of Re-186(Sn)HEDP at 2-month intervals. Each experienced a sustained decrease in both pain and analgesic intake. The only evident clinical or biochemical toxicity was a mild progressive decline in their total platelet counts.

Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in skeletal metastases in patients with advanced cancer. A single intravenous administration of approximately 34 mCi (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable patients (77%) following the initial injection, and in 7 of 14 evaluable patients (50%) following a second treatment. Patients responding to treatment experienced an average decrease in pain of about 60%, with one in five treatments resulting in a complete resolution of pain. The only adverse clinical reaction was the occurrence after about 10% of the administered doses of a mild, transient increase in pain within a few days following injection. Statistically significant but clinically unimportant decreases in total white blood cell counts and total platelet counts were observed within the first 8 weeks following the injection; no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for the palliation of painful skeletal metastases.

Rhenium-186 (tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that simultaneously localizes in multiple skeletal metastases in patients with advanced cancer. A single intravenous administration of 30-35 mCi (1110-1295 MBq) is associated with a prompt, significant relief of osseous pain in about 80% of such patients. The efficacy of this new compound was evaluated further by utilizing a double-blind crossover comparison with 99mTc-methylene diphosphonate (MDP) as a radioactive placebo. The new rhenium compound resulted in a significantly (p less than 0.05) greater decrease in pain than did treatment with the radioactive placebo. Rhenium-186(Sn)HEDP appears to be a useful new compound for the palliation of painful skeletal metastases.

131I continues to be one of the safest and most effective methods of diagnosing and treating metastatic well differentiated thyroid cancer. It is not without risk, however, and must be judiciously applied to carefully prepared and selected patients.

Rhenium-186(tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in areas of osseous metastases in a manner similar to that of standard bone-scanning agents. It also emits beta particles with sufficient energy to be therapeutically useful. A single intravenous injection of about 33 mCi (1,221 MBq) was given to each of 20 elderly patients with advanced skeletal metastases from hormonally resistant prostate cancer. Prompt, significant relief of pain occurred 80% of the time with no significant side effects and only minimal, transient marrow toxicity. Re-186(Sn) HEDP appears to be a useful new agent for the palliation of painful osseous metastases in prostate cancer.

Thyroid nodularity following continuous low-dose radiation exposure in China was determined in 1,001 women aged 50-65 years who resided in areas of high background radiation (330 mR/yr) their entire lives, and in 1,005 comparison subjects exposed to normal levels of radiation (114 mR/yr). Cumulative doses to the thyroid were estimated to be of the order of 14 cGy and 5 cGy, respectively. Personal interviews and physical examinations were conducted, and measurements were made of serum thyroid hormone levels, urinary iodine concentrations, and chromosome aberrations in circulating lymphocytes. For all nodular disease, the prevalences in the high background and control areas were 9.5% and 9.3%, respectively. For single nodules, the prevalences were 7.4% in the high background area and 6.6% in the control area (prevalence ratio = 1.13; 95% confidence interval = 0.82-1.55). There were no differences found in serum levels of thyroid hormones. Women in the high background region, however, had significantly lower concentrations of urinary iodine and significantly higher frequencies of stable and unstable chromosome aberrations. Increased intake of allium vegetables such as garlic and onions was associated with a decreased risk of nodular disease, which seems consistent with experimental studies suggesting that allium compounds can inhibit tumor growth and proliferation. The prevalence of mild diffuse goiter was higher in the high background radiation region, perhaps related to a low dietary intake of iodine. These data suggest that continuous exposure to low-level radiation throughout life is unlikely to appreciably increase the risk of thyroid cancer. However, such exposure may cause chromosomal damage.

Thirty patients had bone scintigraphy with both Tc-99m pyrophosphate (Tc-PPi) and Tc-99m diphosphonate (Tc-HEDP). The images were given a composite rating for quality and the basis of three sets of criteria, and were also compared for the number of lesions detected by each agent. The two agents provided no difference in scan quality. Nevertheless, in ten of the 30 patients, at least two of the three readers detected with Tc-HEDP lesions that were not seen with Tc-PPi, and in two such cases all three readers considered the Tc-PPi scan normal. In another of these ten, two of three readers felt the Tc-PPi image was norm, whereas all three detected the lesion with Tc-HEDP. The reverse never occurred (P less than 0.01).