Low correlation between serum thyroglobulin and 131I radioiodine whole body scintigraphy: implication for postoperative disease surveillance in differentiated thyroid cancer.

PURPOSE: To evaluate postoperative serum thyroglobulin (Tg) as a reliable tumor marker in low-risk differentiated thyroid cancer (DTC). METHODS: Two hundred and three patients met the selection criteria of >18 years old; who had undergone total or near total thyroidectomy; had a postoperative Tg, and had undergone 131I pre ablation whole body scan (PA-WBS). The primary endpoint was the correlation between Tg level and functional remnant thyroid tissues. Outcomes were categorized as concordant and discordant. Concordant results were positive Tg (>1 ng/ml) with positive PA-WBS or negative Tg (<1 ng/ml) with negative PA-WBS. Discordant results were negative Tg with a positive PA-WBS or positive Tg with a negative PA-WBS. To increase the sensitivity of Tg detection, we evaluated Tg in patients with high thyroid stimulating hormone (TSH) with serum level >30 mU/l on thyroxine withdrawal protocol. RESULTS: One hundred ten patients (54.1%) had discordant results (p < 0.05) with positive PA-WBS and Tg <1 ng/ml, while 93 patients (45.9%) had concordant results. For concordant results, 88 patients had positive PA-WBS and Tg >1 ng/ml, and 5 patients had negative PA-WBS and Tg <1 ng/ml. There was no patient with Tg >1 ng/ml and negative PA-WBS. There were 74 patients with high TSH (>30 mU/l) on abstention (thyroxine withdrawal protocol). Twenty-four (32.5%) had discordant results (p < 0.001) and 50 (67.5%) had concordant results. CONCLUSION: There is low correlation between postoperative Tg and PA-WBS. The sole use of Tg as a serum biomarker for postoperative disease status may not be reliable.

Single shot lymphoscintigraphy in breast cancer: Effective single tracer sentinel node detection protocol with reduction in procedural pain.

PURPOSE: Variation in protocols for axillary sentinel lymph node (SLN) mapping exists. We strive to evaluate the effectiveness of reduction in number of injections on reducing procedural pain, while maintaining nodal detection. METHODS: Over 7 years, the number of periareolar injections performed was reduced stepwise from 4 to 1. This was analyzed for SLN detection and patients' subjective perceived pain. RESULTS: 828 patients with invasive breast cancer who underwent SLN mapping were included. Laterality of breast injection site included 326 (39.4%) in the right breast, 354 (42.8%) in the left breast and 148 (17.9%) in bilateral breasts. In patients who had 4 injection sites in a unilateral breast (n = 143), the reported pain score was 4.3 ± 2.4. Patients with 3 injections (n = 163), 2 injections (n = 163) and 1 injection (n = 211) in a breast reported pain scores of 3.4 ± 2.4, 3.2 ± 2.2, and 2.9 ± 2.6, respectively. In patients who had bilateral sentinel node procedures, those with 4 injections in each breast for a total of 8 injections (n = 37) reported a pain score of 5.7 ± 2.4. Patients with 3 (n = 51), 2 (n = 31) and 1 (n = 39) injection(s) in each breast reported perceived pain of 4.8 ± 2.8, 3.7 ± 2.7 and 3.5 ± 1.9, respectively. Incremental decreased pain scores were achieved with decreasing number of injections (p < 0.001). Nodal detection was maintained. CONCLUSION: A single periareolar subdermal injection site reduces periprocedural pain while maintaining nodal detection.

Adding value to imaging services: a survey of patient and referring physician preferences for direct radiologic reporting of results.

PURPOSE: To identify preferences of patients and referring physicians for direct patient communication and notification of radiologic study results. METHODS: An anonymous survey was conducted of patients undergoing outpatient radiologic imaging studies and their referring physicians. The voluntary surveys elicited responses regarding preferences on a 5-point Likert scale (Strongly disagree, disagree, neutral, agree and strongly agree), as well as indicated by responding yes or no to specific questions. RESULTS: 368 patients completed the survey. 81.5% of patient responders preferred all results communicated from the radiologist within the same day. 65.9% of patients preferred same day results if normal vs 65.8% if abnormal. 34.5% preferred to wait and review normal results with the referring physician. 41.5% preferred to wait and review abnormal results with the referring physician. It was found that patients were more likely to strongly agree with waiting to review results with the referring physician if the results were abnormal, as opposed to normal (18.5% vs 11.9%, respectively; P < 0.014). 64% of physicians did not want results reviewed with their patients; 87.6% did not want a report sent to the patient by the radiologist, even after report was sent to their office. 66.4% of patients surveyed indicated that waiting for imaging results gives them anxiety. CONCLUSIONS: 58-82% of patients preferred same day radiologist communication of their results while 55-87.6% of physicians did not prefer same day radiologist communication of results directly with their patients. 66.4% of patients surveyed indicated that waiting for imaging results gives them anxiety.

The Use of FDG PET Parametric Imaging in the Diagnosis of Olivopontocerebellar Atrophy.

Olivopontocerebellar atrophy is a rare neurodegenerative syndrome associated with 2 distinct disorders: multiple system atrophy and spinocerebellar ataxia. We present a case involving a 66-year-old man with adult-onset progressing cerebellar signs reflective of a cerebellar syndrome with no significant family history and unremarkable genetic testing for spinocerebellar ataxia. This case was found to be most consistent with sporadic olivopontocerebellar atrophy, which falls under the multiple system atrophy category. This diagnosis can be made using F-FDG PET/CT scanning and with MRI in some cases. However, in this case, relatively new PET/CT quantification and parametric imaging software was used for analysis, CortexID Suite.

Rare Intensely Fluorine-18-fluorodeoxyglucose Avid Large Retropharyngeal Goiter in a Patient with Invasive Breast Carcinoma.

Diffuse increased fluorine-18-fluorodeoxyglucose ((18)F-FDG) avidity on positron emission tomography (PET) scans has been demonstrated in patients with chronic thyroiditis, likely secondary to increased inflammatory cell glucose uptake. A complex association has been demonstrated between breast cancer and thyroid disease, although the mechanism remains elusive. Development of chronic thyroiditis and/or goiter in breast cancer patients has been suggested to convey a more favorable prognosis. Goiter extension is almost exclusively into retrosternal space, with only a handful of cases reported with superior extension into retropharyngeal space. We present a rare case of a diffusely enlarged goiter extending superior and posterior into the retropharyngeal space with an associated intense (18)F-FDG avidity standardized uptake value maximum (SUVmax) of 16.1 in a patient with invasive ductal breast cancer. To our knowledge, this represents the first published case of diffusely (18)F-FDG avid goiter with retropharyngeal extension.

Effects of varying serum glucose levels on 18F-FDG biodistribution.

OBJECTIVE: Hyperglycemia has been shown to influence fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in tumor cells. Therefore, patients are instructed to fast for 6 h, while maintaining serum glucose levels at an acceptable range. The study was performed to evaluate the effect of fasting blood glucose levels on the biodistribution of (18)F-FDG in various tissues including the liver, heart, bone marrow, skeletal muscle, and tumors. MATERIALS AND METHODS: Fingerstick fasting blood glucose is routinely measured on the morning of the procedure. The maximum standardized uptake value (SUV(max)) in the right and left hepatic lobes, left ventricle, sacrum, thigh, and tumor was measured in 229 consecutive patients undergoing (18)F-FDG PET/computed tomography for tumor. Patients were divided into three groups depending on their serum glucose levels: low (<100; n = 53), medium (100-160; n = 149), and high (160-201; n = 27). A retrospective analysis of the relationship between glucose levels and standardized uptake value was performed. RESULTS: There was a statistically significant increase in the average SUV(max) in the right and left hepatic lobes as glucose levels increased (right lobe P=0.00144; left lobe P = 0.03889). Subsequently, pairwise analysis was performed, revealing a statistically significant increase in SUV(max) in the right hepatic lobe between low-glucose and medium-glucose groups and in both hepatic lobes between low and high groups (P < 0.017). No significant difference was observed in any of the other measured tissues. CONCLUSION: This study shows a directly proportional relationship between blood glucose levels and nonpathologic (18)F-FDG biodistribution in the right and left hepatic lobes. The influence of blood glucose on expected biodistribution patterns, particularly in the liver, should be considered during interpretation.

FDG-PET-positive lower-extremity sebaceous-gland carcinoma in a patient with Muir-Torre syndrome.

Sebaceous-gland carcinoma can occur alone or as one of the defining features of the Muir-Torre syndrome. Cases occurring below the head and neck are extremely rare. Here we describe the case of a 70-year-old male with Muir-Torre syndrome who had a recurrent sebaceous-gland carcinoma in the left lower extremity that demonstrated (18)F-FDG avidity. An (18)F-FDG-avid lower-extremity sebaceous-gland carcinoma has not been previously reported.

Pediatric osteomyelitis: a scintigraphic case-based review.

This review presents techniques to optimize bone scintigraphy for evaluation of the spectrum of abnormalities associated with pediatric osteomyelitis, with an emphasis on the approaches to patient preparation and positioning and to interpretation. The diagnosis of pediatric osteomyelitis can be challenging for several different reasons. Bone scintigraphy is especially useful when the site of osteomyelitis is unclear. Other imaging modalities, including radiography, ultrasonography, and magnetic resonance imaging, all have advantages and may have a role in evaluating the condition of the child with osteomyelitis. Pathophysiologic considerations unique to children contribute to a different clinical presentation of osteomyelitis in the pediatric population than that seen in adults. In addition, patient movement degrades image quality substantially, which is an important consideration for imaging children. Neonates have a higher incidence of multifocal osteomyelitis, and they represent a unique subset of the pediatric population with separate considerations. Several examples illustrate techniques to optimize imaging, as well as show the spectrum of abnormalities associated with pediatric osteomyelitis. Careful attention to bone scintigraphic technique ensures that high-quality images can be obtained, which will allow confident diagnosis of pediatric osteomyelitis.

Right upper quadrant pain and mass in a 41-year-old previously healthy man: a presenting feature of HIV-associated extranodal diffuse large B cell lymphoma with cardiac involvement.

With an increasing pandemic of HIV/AIDS, the incidence of HIV-associated lymphoma is expected to rise. Here, the authors report a case of a 41-year-old man who presented with right upper quadrant pain and mass, and was subsequently diagnosed with HIV-associated diffuse large B cell lymphoma (DLBCL) with cardiac involvement. This case illustrates some of the uncommon and interesting aspects of DLBCL: primary extramedullary extranodal stage IV disease as the presenting feature; cardiac involvement at presentation; DLBCL as the only clue to the diagnosis of HIV; and management of HIV-associated DLBCL. This case is also a reminder of the importance of the routine HIV screening for all patients between the ages of 13-64 years, as advocated by centres of disease control and prevention.

Does hormonal therapy have a therapeutic role in metastatic primary small cell neuroendocrine breast carcinoma? Case report and literature review.

Primary neuroendocrine carcinoma of breast (NECB) is a very rare tumor; the World Health Organization(WHO) subcategorized these tumors into 3 major histologic subtypes: solid, small cell carcinoma (SMCC), and large cell NE carcinoma. The SMCC subtype is the least common and most aggressive and has been reported to be as aggressive as its pulmonary counterpart. SMCC is usually confirmed based on clinical, pathologic,and imaging studies. Local disease is usually managed in a fashion similar to that of the usual ductal breast cancer; in the metastatic SMCC setting, regimens that are implemented in small cell lung cancer are usually attempted, according to case reports and published small case series. Hormone receptors can be expressed in more than 90% of the solid tumor subtype; however its expression is manifested in about 50% of cases of SMCC. Although hormonal therapy can be used successfully to treat the usual metastatic ductal breast cancer,its utility in metastatic SMCC has not been reported. We report an impressive response to hormonal therapy in a patient with late relapse of breast carcinoma with a metastatic SMCC subtype that expressed hormone receptors. The response to hormonal therapy was sustained for about 12 months. The response to hormonal therapy is definitely an interesting finding that, to our knowledge, has not been described before in the setting of metastatic SMCC. We suggest considering adding hormonal therapy to the treatment pipeline for primary SMCC of the breast that express hormone receptors.

The bone scan.

Bone imaging continues to be the second greatest-volume nuclear imaging procedure, offering the advantage of total body examination, low cost, and high sensitivity. Its power rests in the physiological uptake and pathophysiologic behavior of 99m technetium (99m-Tc) diphosphonates. The diagnostic utility, sensitivity, specificity, and predictive value of 99m-Tc bone imaging for benign conditions and tumors was established when only planar imaging was available. Currently, nearly all bone scans are performed as a planar study (whole-body, 3-phase, or regional), with the radiologist often adding single-photon emission computed tomography (SPECT) imaging. Here we review many current indications for planar bone imaging, highlighting indications in which the planar data are often diagnostically sufficient, although diagnosis may be enhanced by SPECT. (18)F sodium fluoride positron emission tomography (PET) is also re-emerging as a bone agent, and had been considered interchangeable with 99m-Tc diphosphonates in the past. In addition to SPECT, new imaging modalities, including (18)F fluorodeoxyglucose, PET/CT, CT, magnetic resonance, and SPECT/CT, have been developed and can aid in evaluating benign and malignant bone disease. Because (18)F fluorodeoxyglucose is taken up by tumor cells and Tc diphosphonates are taken up in osteoblastic activity or osteoblastic healing reaction, both modalities are complementary. CT and magnetic resonance may supplement, but do not replace, bone imaging, which often detects pathology before anatomic changes are appreciated. We also stress the importance of dose reduction by reducing the dose of 99m-Tc diphosphonates and avoiding unnecessary CT acquisitions. In addition, we describe an approach to image interpretation that emphasizes communication with referring colleagues and correlation with appropriate history to significantly improve our impact on patient care.

A phase I trial combining high-dose 90Y-labeled humanized anti-CEA monoclonal antibody with doxorubicin and peripheral blood stem cell rescue in advanced medullary thyroid cancer.

UNLABELLED: This trial determined the pharmacokinetics, dosimetry, and dose-limiting toxicity of 90Y-hMN-14 IgG (humanized anticarcinoembryonic antigen [CEA, or CEACAM5] monoclonal antibody; labetuzumab), combined with doxorubicin and peripheral blood stem cell (PBSC) support in advanced medullary thyroid cancer (MTC) patients. METHODS: Fifteen patients received an infusion of 111In-hMN-14 IgG. One to 2 wk later, 14 patients received 90Y-hMN-14 IgG, starting at 740 MBq/m2, followed 24 h later with a fixed intravenous bolus dose of doxorubicin (60 mg/m2). Preharvested PBSCs were reinfused when the 90Y activity in the body was < or =111 MBq/m2. RESULTS: The mean red marrow dose estimated for the 90Y-hMN-14 IgG was 1.65 +/- 0.59 mGy/MBq (n = 11), with normal organs ranging from approximately 2.3 to 4.4 mGy/MBq. Eighty percent of all known lesions (125/156), including 78 of 79 bone and 16 putatively occult lesions, were targeted. The average radiation dose to the tumor was 15.1 +/- 10.8 mGy/MBq (55.8 +/- 39.8 cGy/mCi) 90Y-hMN-4 IgG (n = 29 tumors in 8 patients), with a majority of the lesions receiving >2,000 cGy at an administered dose of < or =1,480 MBq/m2. The average tumor-to-red marrow, tumor-to-liver, tumor-to-lungs, and tumor-to-kidneys ratios were 15.0 +/- 11.0, 5.1 +/- 3.6, 6.9 +/- 6.1, and 9.0 +/- 8.7, respectively. Cardiopulmonary toxicity was dose limiting at 1,850 MBq/m2. Minor responses were noted in 2 patients and 1 patient had a partial response (68% reduction in local and hepatic metastatic disease). CONCLUSION: This treatment combination was well tolerated with complete recovery of blood counts and reversible nonhematologic toxicities at the maximum tolerated dose of 1,480 MBq/m2. Evidence of antitumor response in these patients with advanced cancer was modest, but encouraging; this type of treatment may be more successful if applied to more limited, earlier-stage disease.

Radioimmunotherapy of non-Hodgkin's lymphoma with 90Y-DOTA humanized anti-CD22 IgG (90Y-Epratuzumab): do tumor targeting and dosimetry predict therapeutic response?

UNLABELLED: A DOTA (1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid)-conjugated, (111)In- and (90)Y-labeled humanized antibody to CD22, epratuzumab, was studied in patients with non-Hodgkin's lymphoma (NHL) to assess biodistribution and tumor targeting, pharmacokinetics, dosimetry, and anti-antibody response. Of particular interest was to evaluate whether pretherapy targeting and tumor dosimetry could predict therapeutic responses. METHODS: Patients received a pretherapy imaging study with (111)In-DOTA-epratuzumab IgG (0.75 mg/kg), followed about 1 wk later with (90)Y-DOTA-epratuzumab starting at a dose level of 0.185 GBq/m(2) (5 mCi/m(2)) in patients who had prior high-dose chemotherapy (group 2), and at 0.370 GBq/m(2) in patients who did not have a prior transplant (group 1), with escalation in 0.185-GBq/m(2) increments. RESULTS: The effective blood half-life for (111)In-DOTA epratuzumab was 36.1 +/- 7.9 h (n = 25) compared with 35.2 +/- 7.0 h for (90)Y-DOTA-epratuzumab (n = 22). The whole-body half-life for (90)Y-DOTA-epratuzumab estimated from (111)In-DOTA-epratuzumab scintigraphy was 58.3 +/- 4.7 h (n = 20), with urine collection confirming the loss of between 2.2% and 15.9% of the injected activity over 3 d (n = 3). One-hundred sixteen of 165 CT-confirmed lesions were visualized with (111)In-DOTA-epratuzumab. Radiation-absorbed doses to liver, lungs, and kidneys averaged 0.55 +/- 0.13 (n = 17), 0.28 +/- 0.06 (n = 17), and 0.38 +/- 0.07 mGy/MBq (n = 10), respectively, with 0.14 +/- 0.02 and 0.23 +/- 0.04 mGy/MBq delivered to the whole-body and red marrow, respectively. Tumor doses (n = 14 lesions in 10 patients) ranged from 1.0 to as much as 83 mGy/MBq for a 0.5-g lesion (median, 7.15 mGy/MBq). Group 2 patients were more likely to experience significant hematologic toxicities, but doses of up to 0.370 GBq/m(2) of (90)Y-DOTA-epratuzumab were tolerated with standard support measures, whereas patients in group 1 tolerated doses of up to 0.740 GBq/m(2) with the potential for further escalation. Anti-tumor effects were seen in both indolent and aggressive NHL. The data also suggest that anti-tumor responses of potentially equal magnitude can occur irrespective of tumor targeting and tumor size. Hence, tumor response did not correlate with the radiation dose delivered or with the tumor being visualized by external imaging. An anti-antibody response to epratuzumab was detected by an enzyme-linked immunosorbent assay in only 2 of 16 patients. CONCLUSION: These results suggest that (90)Y-DOTA-epratuzmab is a promising agent for the treatment of NHL and warrants further study. There was evidence suggesting that in this system, factors other than tumor radiation dose and targeting may be involved in the success of radioimmunotherapy.

Red marrow radiation dose adjustment using plasma FLT3-L cytokine levels: improved correlations between hematologic toxicity and bone marrow dose for radioimmunotherapy patients.

UNLABELLED: Calculated red marrow absorbed dose in patients receiving radioimmunotherapy (RAIT) has not been highly predictive of the dose-limiting hematologic toxicity observed in many patient populations studied. Because patients receiving the same red marrow dose often experience different grades of toxicity, other factors might help predict the different grades of toxicity observed. One such factor may be the plasma FLT3-L (FMS-related tyrosine kinase 3 ligand, hematopoiesis stimulatory cytokine) level, which has been shown to be a better indicator of recovery of progenitor cells and, thus, red marrow radiosensitivity (because during the recovery period the progenitor cells are hyperproliferative and potentially more radiosensitive) for patients treated with previous chemotherapy than peripheral blood counts. METHODS: Red marrow radiation doses were determined for 30 patients (20 male, 10 female; all without bone marrow or bone involvement; 19 had prior chemotherapy) after receiving (131)I RAIT (activity range, 2.1-8.9 GBq) for treatment of solid cancers known to produce carcinoembryonic antigen. Radiation dose estimates were calculated using 2 different methods of red marrow cumulated activity and red marrow-to-blood activity concentration ratio determinations for 2 dosimetric models: using both male and female and male-only masses and S values. Highest platelet toxicity grade at nadir (PTG), percentage platelet decrease (PPD) in counts, and platelet nadir (PN) counts were measured. FLT3-L levels (pg/mL) were determined by immunoassay before treatment; a normal FLT3-L level was assumed to be 80 pg/mL. The red marrow radiation doses (cGy) were adjusted for the patient's FLT3-L level when the patient's cytokine level exceeded the normal value. Marrow doses and FLT3-L-adjusted marrow doses were correlated with PTG, PPD, PN, and 1/PN. Administered activity, administered activity per unit body weight, and total body radiation dose were also correlated with these hematologic toxicity measures. RESULTS: All red marrow dose calculation schemes resulted in essentially the same correlations for a given hematologic toxicity measure. Poor correlations were observed between administered activity, administered activity per unit body weight, total body radiation dose, or red marrow radiation dose and PTG, PPD, PN, and 1/PN. All correlations improved greatly when the various predictors of toxicity were adjusted for the patient's FLT3-L level. The highest correlation observed was between red marrow dose or total body dose and 1/PN (r = 0.86). Using an unadjusted red marrow dose to predict toxicity >/= grade 3, there were 8 true-positive, but 13 false-positive cases with 9 true-negatives. However, using a FLT3-L-adjusted red marrow dose, there were 8 true-positives, but only 2 false-positives and 20 true-negatives. CONCLUSION: FLT3-L-adjusted red marrow radiation doses provide improved correlation with hematologic toxicity. Thus, elevated FLT3-L plasma levels before RAIT may indicate increased radiosensitivity of the bone marrow, and use of this measurement to adjust calculated red marrow or total body radiation doses may provide significantly better prediction of toxicity than radiation dose alone, leading to a patient-specific administered activity prescription that will deliver radiation doses to diseased tissues sufficient to produce an effective treatment outcome at acceptable toxicity levels.

Phase I radioimmunotherapy trial with iodine-131--labeled humanized MN-14 anti-carcinoembryonic antigen monoclonal antibody in patients with metastatic gastrointestinal and colorectal cancer.

This trial was conducted to determine the pharmacokinetics, dosimetry, dose-limiting toxicity, and the maximum tolerated dose of iodine-131 humanized MN-14 immunoglobulin G (131I-hMN-14 IgG), a humanized complementary-determining region-grafted anti-carcinoembryonic antigen monoclonal antibody, in metastatic gastrointestinal and colorectal cancer patients. Patients were divided into 2 groups: group A consisted of patients who had prior external beam radiation therapy (n = 8), and group B included patients who had received standard chemotherapy (n = 13). All patients received a diagnostic infusion of 131I-hMN-14 IgG (approximately 8.0 mCi, 15 mg/m2) to study the pharmacokinetics, biodistribution, and dosimetry. One week later, 17 of 21 patients received infusional therapy of escalating radioactive doses of 131I-hMN-14 IgG. Blood pharmacokinetics and quantitative imaging were performed again after the therapeutic dose. Radiation-absorbed doses to normal organs and tumors were determined by MIRDOSE-3 algorithms. The primary dose-limiting toxicity was hematologic toxicity at 40 mCi/m2. The blood half-life (n = 20) was identical for the diagnostic and therapy infusions. The mean red marrow dose was 2.2 +/- 2.4 cGy/mCi. The mean tumor radiation dose (n = 8) was 24.2 +/- 22.6 cGy/mCi. Tumor targeting was seen in most large metastatic lesions. No objective responses were seen in these heavily pretreated and mostly advanced patients. In conclusion, 131I-hMN-14 IgG has good targeting, good tumor to normal organs radiation absorbed ratios, and an acceptable toxicity profile in advanced metastatic gastrointestinal and colorectal cancer patients.