Dual-tracer radionuclide imaging in hyperparathyroidism: thallium-201 parathyroid scintigraphy revisited.

OBJECTIVES: Tc-sestamibi is the current radiopharmaceutical of choice for the localization of hyperactive lesions of the parathyroid glands in patients with hyperparathyroidism. However, there are multiple factors that adversely affect the accumulation and retention Tc-sestamibi in the hyperfunctioning parathyroid tissue, resulting in a false-negative scan. The objective of this study was to investigate the possibility of an incremental diagnostic role of thallium-201 parathyroid scintigraphy in patients with presumably false-negative Tc-sestamibi scan results. PATIENTS AND METHODS: The study comprised of 22 patients including 16 with primary hyperparathyroidism (PHPT) and 6 with secondary hyperparathyroidism where Tc-sestambi scan was initially negative, inconclusive or where additional lesions were suspected on the single-photon computed tomography/computed tomography (SPECT/CT) scan with the CT component identifying lesion(s) without significant Tc-sestamibi uptake. RESULTS: The results of our study show that in 22 patients (5 male, 17 female; age range 26-81; median age 53.4) further imaging with thallium-201 SPECT/CT scan showed 46.5% additional lesions in patients with hyperparathyroidism caused by an adenomatous or hyperplastic parathyroid lesion. In patients with PHPT caused by an adenomatous or hyperplastic parathyroid lesion, further imaging with thallium-201 showed 59% additional hyperactive parathyroid lesions. In patients with secondary hyperparathyroidism, further imaging with thallium-201 SPECT/CT showed additional 33.3% hyperplastic parathyroid lesions. CONCLUSION: The results of this pilot study strongly advocate a role for thallium parathyroid SPECT/CT imaging in patients with primary and secondary hyperparathyroidism where the initial Tc-sestamibi scan is deemed to be false-negative in the presence of biochemical hyperparathyroidism.

PET/CT Dose Planning for Volumetric Modulated Arc Radiation Therapy (VMAT) -Comparison with Conventional Approach in Advanced Prostate Cancer Patients.

Molecular imaging is the only way of defining biological target volume (BTV) for externalbeam radiation therapy (EBRT) and may be used for advanced targeting in dose planning and dose painting. There are, however, no reports about the EBRT response when dose planning is based on BTV target definition in advanced prostate cancer. Clinical and biochemical results of two clinically equal group of patients with advanced prostate cancer patients were compared. Both groups were treated with volumetric modulated arc therapy (VMAT) based on target definition by PET/CT (1(st) group) or conventional imaging (2(nd) group). Biochemical relapse occurred in 16.6% (in 1 out of 6) of the patients in the first group and 50% (3 out of 6) patients in the second group during the follow up period. Clinical manifestation of disease occurred in 33% (2 out of 6) patients of the first group and in 5 out of 6 (83,3%) patients in the second one. 4 patients in the first group had no biochemical relapse and no clinical manifestation during the follow up period. The difference in the duration of progression free period was statistically significant between the groups (p<0.010) being in the first group 16.5±5.4 (10-24) months and 4.6±2.9 (2-10) months in the second one. Because patients with PET/CT based VMAT had lower incidence of biochemical relapse, less clinical manifestations and longer, statistically significant duration of progression free period as compared to patients treated with VMAT based on conventional imaging, our preliminary results suggest introducing BTV definition based on PET imaging for VMAT in the EBRT of prostate cancer.

Evaluation of Alpha-Therapy with Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer-the Role of Gamma Scintigraphy in Dosimetry and Pharmacokinetics.

Radium-223-dichloride ((223)RaCl2) is a new bone-seeking calcium analogue alpha-emitter, which has obtained marketing authorization for the treatment skeletal metastases of hormone-refractory prostate cancer. The current treatment regimen is based on six consecutive doses of (223)RaCl2 at 4 week intervals and the administered activity dose, 50 kBq/kg per cycle is based on patient weight. We analyzed two patients using quantitative serial gamma imaging to estimate dosimetry in tumors and see possible pharmacokinetic differences in the treatment cycles. The lesions were rather well visualized in gamma scintigraphy in spite of low gamma activity (<1.1% gamma radiation) at 0, 7 and 28 days using 30-60 min acquisition times. Both our patients analyzed in serial gamma imagings, had two lesions in the gamma imaging field, the mean counts of the relative intensity varied from 27.8 to 36.5 (patient 1), and from 37.4 to 82.2 (patient 2). The half-lives varied from 1.8 days to 4.5 days during the six cycles (patient 1), and from 1.5 days to 3.6 days (patient 2), respectively. In the lesion half-lives calculated from the imaging the maximum difference between the treatment cycles in the same lesion was 2.0-fold (1.8 vs. 3.6). Of these patients, patient 1 demonstrated a serum PSA response, whereas there was no PSA response in patient 2. From our data, there were maximally up to 4.0-fold differences (62.1 vs. 246.6 ) between the relative absorbed radiation doses between patients as calculated from the quantitative standardized imaging to be delivered in only two lesions, and in the same lesion the maximum difference in the cycles was up to 2.3-fold (107.4 vs. 246.6). Our recommendation based on statistical simulation analysis, is serial measurement at days 0-8 at least 3 times, this improve the accuracy significantly to study the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the imaging. Both our patients had originally two metastatic sites in the imaging field; the former patient demonstrated a serum PSA response and the latter demonstrated no PSA response. In these two patients there was no significant difference in the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the quantitative imaging. Our results, although preliminary, suggest that dose monitoring can be included as a part of this treatment modality. On the other hand, from the absorbed radiation doses, the response cannot be predicted because with very similar doses, only the former patient responded.

Preliminary clinical experience of trans-1-Amino-3-(18)F-fluorocyclobutanecarboxylic Acid (anti-(18)F-FACBC) PET/CT imaging in prostate cancer patients.

BACKGROUND: In this retrospective analysis we assessed the role of [(18)F]-FACBC-PET/CT in the prostatic cancer staging. PROCEDURE: 30 first [(18)F]-FACBC-PET/CT images of 26 patients (68.1 ± 5.8 years) were analyzed. PET/CT findings were compared with PSA concentrations, with PSA doubling times (PDT), and with correlative imaging. RESULTS: On 16 [(18)F]-FACBC (53.3%) scans, 58 metabolically active lesions were found. 12 (20.7%) lesions corresponding to the local relapse were found in prostate/prostate bed and seminal vesicles, 9 (15.5%) lesions were located in regional lymph nodes, 10 (17.2%) were located in distal lymph nodes, and 26 (44.8%) metabolically active lesions were found in the skeleton. In one case, focal uptake was found in the brain, confirmed further on MRI as meningioma. The mean S-PSA level in patients with positive [(18)F]-FACBC findings was 9.5 ± 16.9 µ g/L (0.54-69 µ g/L) and in patients with negative [(18)F]-FACBC findings was 1.96 ± 1.87 µ g/L (0.11-5.9 µ g/L), but the difference was not statistically significant. However, the PSA doubling time (PDT) in patients with positive findings was significantly shorter than PDT in patients with negative findings: 3.25 ± 2.09 months (0.3-6 months) versus 31.2 ± 22.02 months (8-84 months), P < 0.0001. There was a strong positive correlation between PSA value and number of metabolically active lesions (R = 0.74) and a negative correlation between PDT and number of metabolically active lesions (R = -0.56). There was a weak negative correlation between PDT and SUVmax⁡ (R = -0.30). CONCLUSION: According to our preliminary clinical experience, [(18)F]-FACBC-PET may play a role in in vivo restaging of an active prostate cancer, especially in patients with a short S-PSA doubling time.

Radionuclide Treatment with 153Sm-EDTMP is Effective for the Palliation of Bone Pain in the Context of Extensive Bone Marrow Metastases: A Case Report.

Radionuclide therapy is widely used as an effective modality in the management of bone pain. The main indication for this treatment is symptomatic bone metastases, confirmed by bone scintigraphy. We present a case of small cell lung cancer (SCLC) stage T4N2M1b, with a good metabolic response to systemic therapy and radiotherapy of the primary tumor and locoregional disease, which became metabolically less active and remarkably smaller in size (reduction to 1/6 of the original volume). In spite of the good overall response, the patient developed a syndrome with severe bone pain and had progression in the bone marrow metastases, confirmed by (18)F-FDG PET/CT. The patient received (153)Sm-EDTMP treatment with a good clinical response. However, in the whole body bone scan with the therapeutic dose, there was no visual evidence of bone metastasis. Retrospectively, by drawing the region of interest, it was possible to identify one metastatic site. The possible mechanisms of the efficacy of this treatment modality, in this specific setting, are also discussed.

Optimal timing of bisphosphonate administration in combination with samarium-153 oxabifore in the treatment of painful metastatic bone disease.

While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide therapy is widely used for treatment of painful bone metastases. Combined radionuclide therapy with bisphosphonates has demonstrated improved effectiveness in achieving bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates alone. However, there are conflicting reports as to whether bisphosphonates adversely influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline study, as well as in combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not provide any statistically significant difference in urinary excretion of Sm-153 between the two groups. It may be noted that the exact temporal sequence of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied. One of the side effects of bisphosphonates is transient flare effect on bone pain. Radionuclide therapy may also have similar side effect. Keeping in view the above the current study was designed with the main objective of determining the exact timing of bisphosphonate administration in patients receiving combined therapy so as to achieve optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP) and Zoledronic acid were divided into three groups according to the timing of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid 7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153 oxabifore was administered to all patients at the standard bone palliation dose of 37 MBq/kg body weight. All patients received Zoledronic acid before and after treatment in standard dosage of 4 mg every 28 days. WB bone scan, CT, and MRI were performed before treatment in all patients to exclude cord compression and vertebral fractures. Pain scores and quality of life (QOL) measurements were recorded meticulously in all patients. In groups I, II, and III, pain relief occurred in 10.4 ± 3.1 (Range = 5-15); 3.1 ± 1.1 (Range = 1-5) and 22 ± 5.1 (Range = 15-35) days, respectively, following radionuclide therapy. There was statistically significant difference between pain score in all groups before and after treatment as well as statistically significant difference in time to pain relief onset between Group II and other groups of patients (P < 0.0001). Based on our results we concluded that administration of Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment helps in achieving better pain relief, as well as at the shortest time interval from the start of therapy.

Effectiveness of bone metastases treatment by sm-153 oxabifore in combination with monoclonal antibody denosumab (xgeva): first experience.

Breast and prostate cancer have a propensity to metastasize to bones and cause osteolysis and abnormal new bone formation. Metastases locally disrupt normal bone remodeling. Although metastases from prostate cancer have been classified as osteoblastic based on the radiographic appearance of the lesion, data gleaned from a rapid autopsy program indicate that the same prostate cancer patient may have evidence of both osteolytic and osteoblastic disease as shown by histologic examinations. Thus, bone metastases are heterogeneous, requiring combined treatment targeting on both osteolytic and osteoblastic lesions. While Samarium-153 (Sm-153) oxabifore treatment is widely used for the relief of pain in patients with osteoblastic metastatic bone lesions, Xgeva (Denosumab) is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. It is a fully human monoclonal antibody that has been designed to target receptor activator of nuclear factor-kB ligand (RANKL), a protein that acts as the primary signal to promote bone removal. In many bone loss conditions, RANKL overwhelms the body's natural defense against bone destruction. The main objectives of the current pilot study were to estimate the effectiveness of bone metastases treatment by a combination of Sm-153 oxabifore and Xgeva (Denosumab). Five patients (four female and one male, aged 35-64, mean age 50.8) with multiple skeletal metastases from prostatic carcinoma (1) and breast carcinoma (4) were studied. Their mean objective pain score according to visual analog scoring system on a 1-10 scoring system was 7.8 ± 0.5 (range 6-9). Sm-153 oxabifore was administered at the standard bone palliation dose of 37 MBq/kg body weight. Xgeva (Denosumab) was administered at a dosage of 120 mg every 4 weeks, with the monitoring of calcium level and administration of calcium, magnesium, and vitamin D. Whole body (WB) bone scan was performed before and 3 months after treatment in all patients. After Sm-153 oxabifore administration, pain relief occurred within 4.4 ± 1.25 days (range 2-9 days) and the objective pain score decreased to 0.2 ± 0.2 (range 0-1). There was statistically significant difference found, according to the pain score system, before and after treatment (P < 0.0001). WB bone scan showed that in one patient, there was significant reduction in the number and intensity of bone metastases, and in four patients, there was no evidence of bone metastases found. Based on our first experience, combined treatment of bone metastases with Sm-153 oxabifore and Denosumab is effective and safe.

Observed influence of nitroglycerine on myocardial perfusion scintigraphy in patients with multiple vessel coronary artery disease and well-developed collaterals.

The objective of this scientific work was to evaluate the extent and severity of perfusion abnormalities on myocardial perfusion scintigraphy (MPS) at rest and with sublingual nitroglycerine, in relation to the presence and anatomical location of collaterals demonstrated by selective coronary angiography (SCA). Twenty-eight patients with unstable angina underwent selective coronary angiography. Eighteen of them were diagnosed with myocardial infarction (MI) 2-15 days prior to examination. Presence or absence of collaterals was noted, with anatomical depiction of donor and recipient arteries as well as evaluation of degree of collateral flow. As an inclusion criterion, collateral flow had to be grade 2 (partial epicardial filling of the occluded artery) or 3 (complete epicardial filling of the occluded artery) in accordance with the Rentrop collateral flow classification. Flow was noted as follows: Complete antegrade (CA), complete retrograde (CR), partial antegrade (PA), and partial retrograde (PR). Myocardial perfusion scintigraphy using Tc-99m Sestamibi at rest and after sublingual administration of nitroglycerine was performed according to a 2-day protocol. Perfusion abnormalities, which were quantified using the 20-segments model and visual 5-point system (0, normal perfusion; 4, absent perfusion), were analyzed according to donor's and recipient's territories, as well as territories with limited or without collateral flow (PA/PR, grade 0-1 flow). A total of 84 arteries were analyzed, with stenosis in 79 of them. Arteries were divided into three groups: Donors (group I), recipients (group II), and arteries with limited or without collaterals (group III). In group I, there were 28 donor arteries, with mean severity of stenosis 71.3 ± 0.65%. In group II, there were 36 recipient arteries and mean severity of stenosis was 94.8 ± 0.26%. In group III, there were 20 arteries, and all of them had either no or poorly developed collaterals (mean severity of stenosis 60.4 ± 2%). In 3 cases, 2 donor arteries gave collaterals to 1 recipient artery, while in 11 cases, a single donor artery gave collaterals to 2 recipient arteries, and in 11 cases there was 1 donor to 1 recipient artery. A total of 1120 MPS segments were analyzed (560 at rest and 560 after nitroglycerine). The number of segments in groups I, II, and III were 204, 242, and 144, respectively. Mean number of segments per donor artery was 7.2 ± 0.7, mean number of segments per recipient artery was 7.0 ± 0.3, and mean number of segments in the territory of arteries without collaterals was 5.5 ± 0.5. In the territory of donor arteries, the mean number of segments with normal, decreased, and absent perfusion at rest was 1.6 ± 0.07, 5.67 ± 0.07, and 0.6 ± 0.03, respectively. After nitroglycerine administration, the mean number of above-mentioned segments was 1.2 ± 0.07, 6.07 ± 0.06, and 2.3 ± 0.06, respectively. There was no significant difference in the mean number of segments with normal and decreased perfusion at rest and after nitroglycerine administration (P = 0.4). However, the increase of mean segments with absent perfusion that appeared after nitroglycerine administration in donor arteries was statistically significant in comparison to MPS at rest (P < 0.0001). In the territory of recipient arteries, there was statistically significant increase in the mean number of segments with normal perfusion from 0.5 ± 0.02 at rest to 2.7 ± 0.06 with nitroglycerine (P < 0.0001), decrease in mean number of segments with decreased perfusion from 6.5 ± 0.06 at rest to 4.19 ± 0.06 with nitroglycerine (P < 0.0001), and decrease in the mean number of segments with absent perfusion from 2.3 ± 0.06 to 0.7 ± 0.03 (P = 0.003). In Group III, there was increase in mean segments with normal perfusion from 2.4 ± 0.5 to 3.2 ± 0.5, decrease in mean segments with decreased perfusion from 3.15 ± 0.5 to 2.35 ± 0.5, and absent tracer uptake from 1.1 ± 0.5 to 0.45 ± 0.3. However, these changes were not statistically significant (P = 0.3, P = 0.4, and P = 0.2, respectively). There was also statistically significant improvement of perfusion in the recipient territories from mean severity score at rest of 2.67 ± 0.08 to 1.6 ± 0.09 with nitroglycerine (P < 0.0001), in territories of poorly collateralized arteries from mean severity score at rest of 1.5 ± 0.14 to 0.8 ± 0.12 with nitroglycerine (P < 0.0008), as well as significant deterioration of myocardial perfusion in donor artery territories from mean severity score at rest of 1.7 ± 0.06 to 2.4 ± 0.06 with nitroglycerine (P  < 0.0001). Based on the results of the study, we concluded that nitroglycerine administration in patients with multiple vessel coronary artery disease and well-developed collaterals can reduce myocardial perfusion to the areas supplied by donor arteries, even resulting in apparent absent perfusion, probably due to "steal syndrome," although these arteries were less stenosed angiographically and deemed viable on MPS at rest. It appears that MPS in patients on nitroglycerine medication may result in an inappropriate decision by interventionists and surgeons to forgo revascularization. Hence, in cases where large and severe perfusion abnormalities are noted, MPS should be repeated after omitting nitrates.

Clinical significance of myocardial perfusion abnormalities in patients with varying degree of coronary artery stenosis.

OBJECTIVES: (1) To identify myocardial perfusion abnormalities in a cohort of patients having coronary artery disease (CAD) risk factors, with either suspected or clinical evidence of ischaemic heart disease (IHD), and with varying degree of coronary artery stenosis. (2) To evaluate the clinical significance of the extent and severity of perfusion abnormalities assessed by myocardial perfusion scintigraphy (MPS) in relation to the anatomical location of coronary stenosis demonstrated by five-vessel selective coronary angiography (SCA). METHODS: One hundred and thirty-eight patients (106 male, 32 female) with suspected or clinical evidence of IHD underwent diagnostic evaluation at the Central Hospital of Nicosia, between November 2002 and August 2003. The diagnostic work-up included clinical examination, exercise tolerance test, SCA and myocardial perfusion scintigraphy (MPS) using either Tl chloride or Tc-tetrofosmin. RESULTS: Based on the results of SCA, patients were divided into five groups on the basis of stenosis as cross-sectional area of coronary artery lumen and its haemodynamic significance, ranging from group 1=less than 50% coronary stenosis to group 5=100% stenosis (occlusion). Nine of 11 (40.9%) patients with angiographically normal coronary arteries (group 1) had moderate inducible reversible ischaemia on MPS and 9/47 (19.1%) patients with insignificant coronary stenosis (less than 75% stenosis=group 2) had fixed perfusion defects, compatible with previous myocardial infarction. The extent of perfusion abnormalities in post-stress MPS patients from group 2 was not found to be statistically significant (P>0.05) when compared to patients belonging to groups 3, 4 and 5. However, the extent of perfusion abnormalities between patients from group 2, when compared to groups 3, 4 and 5 demonstrated significant statistical difference (P<0.05) on post-rest MPS studies. Furthermore, there was no significant statistical correlation between anatomical location of coronary stenosis and severity of perfusion abnormalities in the corresponding myocardial segments. CONCLUSION: Patients with CAD risk factors, and coronary arteries with insignificant stenosis on angiography, may demonstrate inducible reversible myocardial ischaemia. This is suggestive of coronary endothelial dysfunction. Patients with insignificant coronary artery stenosis and no previous history of adverse coronary events may demonstrate features of previous myocardial infarction on MPS. The severity of perfusion defects demonstrated by MPS may be independent of the anatomical location of coronary artery stenosis.