A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer

A multicentre observational study was conducted by the Italian Association of Nuclear Medicine between 1996 and 1998. Twenty-nine Nuclear Medicine Departments participated. The aims of the study were to systematically evaluate the efficacy, toxicity and repeatability of radionuclide therapy of painful bone metastases (RTBM) in a large number of patients and to assess its incidence in patients with prostate cancer. Out of 818 treatments performed with a single i.v. dose of 148 MBq of strontium-89 chloride or 1,295 MBq of rhenium-186 hydroxyethylidene diphosphonate (HEDP), 610 could be evaluated (527 with 89Sr and 83 with 186Re-HEDP). Eighty-one patients received multiple (up to five) RTBM. The total number of retreatments was 100. Patients were followed up for a period of 3-24 months. Results, assessed according to pain relief and consumption of analgesic drugs, were expressed at four levels: 1, no response; 2, mild response; 3, good response; 4, excellent response. Responses were: level 1 in 19%, level 2 in 21.3%, level 3 in 33.3% and level 4 in 26.4% of cases. Retreatments showed significantly (P<0.01) worse responses (48% levels 3+4), in comparison to first RTBM. Duration of palliation was 5.0+/-3.5 months, and was longer in cases of excellent response, in first RTBM, in patients with limited metastases and when 89Sr was used. Better responses were found in cases of limited skeletal disease, under good clinical conditions, when life expectancy exceeded 3 months, and in radiologically osteoblastic or mixed bone lesions. The only statistically significant predictive factor was life expectancy (P<0.001). Flare phenomenon (14.1% of cases) did not correlate with the response. Haematological toxicity (mild to moderate in most cases) mainly affected platelets, and was observed in 25.5% of cases overall and in 38.9% of retreatments. RTBM did not seem to prolong life, though in some cases scintigraphic regression of bone metastases was observed. The two radiopharmaceuticals did not show any statistically significant differences in palliative efficacy and toxicity, either in first RTBM or in retreatments.     

Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement

This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenias were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of ⁸⁹Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed.     

Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer

Rhenium-186 hydroxyethylidene diphosphonate (¹⁸⁶Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using ¹⁸⁶Re-HEDP Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the ¹⁸⁶Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq ¹⁸⁶Re-HEDP showed grade 3 toxicity (thrombocytes 25–50 × 10⁹/1), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% ± 10% IUA; range: 11%–44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of ¹⁸⁶Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of ¹⁸⁶Re-HEDP has been initiated.     

Radionuclide therapy for painful bone metastases. An Italian multicentre observational study. Writing Committee of an Ad Hoc Study Group.

BACKGROUND: It has been affirmed that observational studies give analogous results to randomised controlled ones. METHODS: A multicentre observational trial was conducted between 1996-1998 in order to evaluate the efficacy of palliative radionuclide therapy for bone metastases in a large number of patients. An evaluation was made on 510 patients with prostate cancer and painful bone metastases, treated with a single iv. dose of 89Sr-chloride (527 treatments) or 186Re-HEDP (83 treatments), in 29 Italian Nuclear Medicine Departments. Eighty-one patients received up to five injections, totalling 100 retreatments. Patients were followed up for a period of 3 months-2 years. Results were expressed at four levels of response: excellent, good, mild, and nil. RESULTS: Responses were excellent in 26.4%, good in 33.3%, mild in 21.3% and nil in 19% of all treatments, while good and excellent responses were obtained in 48% of retreatments. No statistically significant correlations were found between response and age of patients, skeletal extension of tumour, pretherapeutic PSA levels, evidence of non-bony metastases, previous chemotherapy and/or external-beam radiotherapy; osteolytic lesions responded worse than osteoblastic or mixed ones. Hematological toxicity (mild to moderate), mainly affecting platelets, was observed in 25.5% of all treatments and in 38.9% of retreatments. No clear differences were found between the two radiopharmaceuticals employed. CONCLUSIONS: Bearing in mind that observational studies can provide just as accurate results as randomised controlled trials, this study confirms the main findings of various limited monocentre trials.     

FDG-PET, 99mTc-HMPAO white blood cell SPET and bone scintigraphy in the evaluation of painful total knee arthroplasties

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), technetium-99m hexamethylpropylene amine oxime (HMPAO)-labelled white blood cell (WBC) scintigraphy and bone scintigraphy were used in the evaluation of total knee arthroplasties (TKAs). We prospectively included 21 patients who had a three-phase bone scan for exclusion of infection of TKAs. Four hours after injection of 185 MBq ^99mTc-HMPAO-labelled WBCs, planar and single-photon emission tomographic (SPET) imaging was performed. Planar imaging was repeated at 24 h p.i. Consecutively images of the knees were obtained with a dedicated PET system 60 min following the injection of 370 MBq of FDG. Focal tracer uptake was scored on SPET and PET visually (0=no uptake, 4=intense uptake). In addition, SUV (standardised uptake value) per voxel was calculated from attenuation-corrected PET images using the MLAA algorithm. Focal uptake at the bone-prosthesis interface was used as the criterion for infection before and after correlation with the third phase of the bone scan. Final diagnosis was based on operative findings, culture and clinical outcome. In the infected TKAs, the WBC scan showed focal activity of grade 2 (n=2), 3 (n=1) or 4 (n=2). PET scan revealed focal activity of grade 4 (n=5) or 3 (n=1). WBC scan alone had a specificity for infection of 53% [positive predictive value (PPV) 42%, sensitivity 100%], compared with 73% for PET scan (PPV 60%, sensitivity 100%). Considering only lesions at the bone-prosthesis interface that were also present on the third phase of the bone scan, we found a specificity of 93% (PPV 83%) for WBC scan. Using these criteria, a specificity of 80% (PPV 67%) was obtained for PET scan. Two out of three false-positive PET scans were due to loosening of the TKA. It is concluded that WBC scintigraphy in combination with bone scintigraphy has a high specificity in the detection of infected TKAs. FDG-PET seems to offer no additional benefit.     

The role of 99mTc-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response

The occurrence of multidrug resistance (MDR), which is in part due to the overexpression of P-glycoprotein (Pgp), is a major problem in neoadjuvant therapy of malignant musculoskeletal tumours. The aim of this study was to investigate the role of technetium-99m hexakis-2-methoxyisobutylisonitrile (^99mTc-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare ^99mTc-MIBI uptake and washout kinetics with the expression of Pgp and with chemotherapy response. Twenty-five patients (16 males and 9 females, aged between 8 and 65 years) with malignant musculoskeletal tumours were studied. After injection of 555-740 MBq ^99mTc-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were acquired at 10 min and 1 h. From the dynamic images, a tumour perfusion index (TPI) was obtained using Patlak-Rutland analysis. Tumour to background (T/B) ratios of both early and delayed images and percent wash-out rate (WR%) of ^99mTc-MIBI were calculated. Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy, tumour response was assessed by examining the ratio of viable cells and by detecting percent necrosis. Scintigraphic results were compared with Pgp status and therapy response. Irrespective of the Pgp status, all patients showed significant perfusion and ^99mTc-MIBI uptake in early images. There was not a significant correlation between T/B ratios of early and delayed images and Pgp expression. We observed a positive correlation between WR% and Pgp status (r=0.61, P<0.01), and the wash-out rate of ^99mTc-MIBI was significantly higher in patients with high Pgp expression than in those with a low Pgp score (33%Nj% vs 17%Nj%). Therapy response was determined in 21 of 25 patients, and in only 5 of 21 cases was the percent necrosis more than 90%. Neither Pgp expression rate nor WR% was found to show a significant correlation with percent necrosis in the bulk tumour specimens. In conclusion, the initial uptake of ^99mTc-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. A relationship was found between the wash-out rate of ^99mTc-MIBI and the Pgp score, with a significant difference in WR% being observed between patients with high and patients with low Pgp expression.     

EORTC QLQ-BM22 and QLQ-C30 quality of life scores in patients with painful bone metastases of prostate cancer treated with strontium-89 radionuclide therapy

Purpose

Approximately 80?% of patients with prostate cancer will develop bone metastases, which often lead to bone pain and skeletal-related events. Sr-89 is an established alternative for the palliation of bone pain in prostate cancer. We aimed to assess the effect of Sr-89 radionuclide therapy on quality of life (QOL) in prostate cancer patients with painful bone metastases.

Materials and methods

Thirteen patients received a single intravenous injection of Sr-89 at a dose of 2.0?MBq/kg. All patients underwent QOL evaluation prior to Sr-89 treatment and 1, 2, and 3?months afterward using the Japanese version of the EORTC QLQ-BM22, EORTC QLQ-C30, a VAS, and face scale. We also evaluated PSA and ALP response and toxicity of the Sr-89 therapy.

Results

The pain characteristics subscale of the EORTC QLQ-BM22 was significantly reduced from 1?month onward compared with the baseline. The functional interference and psychosocial aspects subscales were significantly higher than baseline from 2?months onward. At 2?months, VAS indicated a significant reduction in pain as compared to the baseline. Sr-89 therapy caused a nonsignificant reduction in PSA and ALP levels. No patients had leukocyte toxicity, and one patient had grade 3 platelet toxicity.

Conclusion

Sr-89 radionuclide therapy can provide not only reduced pain characteristics but also better psychosocial aspects and functional interference in patients with painful bone metastases of prostate cancer.     

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after⁸⁹Sr administration. Patients received 2 MBq/kg (118–148 MBq) of⁸⁹Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%–66% reduction in white cell count and a 14%–75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that⁸⁹Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.     

Palliative analgesic effect of Re-186 HEDP in various cancer patients with bone metastases

The clinical picture of bone metastases is manifested by pain and loss of mechanical stability. Standard treatment options for bone metastases include external beam radiotherapy and the use of analgesics. Due to a large number of lesions in many patients, the use of radionuclide therapy with beta emitters may be preferable. Re-186 hydroxyethylidene diphosphonate (Re-186 HEDP) is one of the radiopharmaceuticals suitable for palliative treatment of metastatic bone pain. The aim of this study was to investigate palliative and side effects of Re-186 HEDP in patients with different types of cancers. MATERIAL & METHOD: Thirty one (17 male, 14 female) patients with various cancers (10 prostate, 10 breast, 4 rectum, 5 lung, 2 nasopharynx) and bone metastases were included in the study. Therapy was started with a fixed dose of 1295 MBq of Re-186 HEDP. If necessary, the same dose was repeated at least 3 times after an interval of 10-12 weeks; A total of 40 standard doses were given; 6 patients received repeated doses (3 doses in 3 patients, 2 doses in 3 patients). The patients with bone marrow suppression were excluded from the study. The pain relief was assessed the Eastern Cooperative Oncologic Group (ECOG) and the Karnofsky status index. All patients were evaluated with standard evaluation forms filled in daily for a maximum of 10 weeks. RESULTS: The mean response rate was 87.5% in patients with breast and prostate cancer, 75% in patients with rectum cancer and 20% in patients with lung cancer. The overall response rate was 67.5%. The palliation period varied between 6 and 10 weeks, with a mean of 8.1+/-1.3 weeks. The maximal palliation effect was observed between the 3rd and 7th weeks. No serious side effects were seen except mild hematologic toxicity. DISCUSSION & CONCLUSION: It is concluded that Re-186 HEDP is a highly effective agent in the palliation of metastatic bone pain in patients with prostate, breast and rectum cancer, but not effective in lung cancer. On the other hand, Re-186 seems to be a good alternative to Sr-89 because of its preferable physical characteristics (such as short half life and gamma energy emission), low side effect profile, early response and repeatability.     

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively ^99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with ^99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent ^99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of ^99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of ^99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of ^99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.     

Effects of ageing on serotonin transporters in healthy females

The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [¹²³I]nor-#-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [¹²³I]nor-#-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P<0.05) was found in the midbrain. The decline in [¹²³I]nor-#-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade).     

89Sr radionuclide therapy: Dosimetry and haematological toxicity in two patients with metastasising prostatic carcinoma

We present dosimetry for spinal metastases and red bone marrow in two patients who received ⁸⁹Sr therapy for disseminated prostatic carcinoma. Absorbed dose to metastases was estimated by combining ⁸⁵Sr gamma camera studies with computed tomographic measurements of bone mass, and doses of 20 cGy/MBq and 24 cGy/MBq were found for vertebral metastases that uniformly involved the bodies of L3 and D12 respectively. Absorbed dose to red bone marrow was estimated from total body strontium retention studies using the ICRP model for bone dosimetry, and a ratio of metastatic to marrow dose of around 10 was found in each patient. Although they received comparable treatment activities of around 200 MBq, the patients showed markedly different haematological response, this difference being confirmed when each received a second ⁸⁹Sr treatment 6 months after the first. As a result, clinically significant thrombocytopenia occurred in one patient which prevented further radiostrontium therapy being given.     

Short- and long-term effects of 186Re-1,1-hydroxyethylidene diphosphonate in the treatment of painful bone metastases.

This study evaluates the short- and long-term therapeutic efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (HEDP) in the palliation of painful bone metastases and the influence of variables before therapy in determining the characteristics of pain palliation. METHODS: Sixty patients with painful bone metastases from different tumor types were treated with 1406 MBq 186Re-HEDP. After treatment, the patients were followed up clinically at weekly intervals for the first month and monthly thereafter up to 1 y, until death or pain relapse. Pain response was graded as complete, partial, minimal, or absent using the Wisconsin test scoring system. Duration of pain relief, performance status, tumor markers, serum alkaline phosphatase levels, hematologic toxicity, and metastatic bone progression were also evaluated. RESULTS: Overall, 80% of individuals experienced prompt relief of pain, with 31% complete, 34% partial, and 15% minimal responses. Transient World Health Organization grade 1-2 hematologic toxicity was apparent, with a decrease in the mean platelet (32%) and mean leukocyte (18%) counts at 3 and 4 wk, respectively. The degree of pain response did not correlate with any pretreatment variable. The duration of pain relief ranged from 3 wk to 12 mo and correlated positively with the degree of response (P = 0.02) and negatively with pretreatment scintigraphic scores and alkaline phosphatase levels (P = 0.02). CONCLUSION: 186Re-HEDP is effective for fast palliation of painful bone metastases from various tumors. The effect tends to last longer if patients are treated early in the course of their disease.     

Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement

This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenias were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of 89Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed.     

Use of technetium-99m HMPAO scintigraphy for the detection of amiodarone lung toxicity in a rabbit model

Amiodarone (AD) is a very effective anti-arrhythmic drug, but its use is often associated with serious pulmonary complications such as pneumonitis and interstitial pulmonary disease. The aim of this study was to investigate the relationship between the amount of amiodarone intake (and the related development of lung toxicity) and the lung uptake of technetium-99m labelled D,L-hexamethylpropylene amine oxime (HMPAO). Eighteen white female New Zealand rabbits were divided into three groups and fed AD by gavage at doses of 10 (group A), 50 (group B) or 150 (group C) mg/kg daily. ^99mTc-HMPAO scintigraphy was performed at baseline and after 1, 2, 3 and 4 weeks of drug intake. Anterior images of 1 min duration were acquired at 30 min after the injection of 37 MBq ^99mTc-HMPAO. Regions of interest (ROIs) were drawn on the lungs (L) and the upper limb (B) as the background. L/B ratios were calculated using the mean counts. In groups A and B histopathological evaluation of the lungs of all rabbits was performed at the end of the 4 weeks of AD intake, while in group C it was performed at 2 weeks because of increased mortality. At baseline, mean L/B ratios for groups A, B and C were 2.8ǂ.3, 2.8ǂ.3 and 2. 8ǂ.4, respectively. After 3 weeks of AD intake, L/B ratios increased to 4.1ǂ.6 and 4.8ǂ.6 in groups A and B, respectively. The L/B ratio was 3.6ǂ.2 after 1 week of AD intake in group C. The correlation coefficients between the lung uptake of ^99mTc-HMPAO and AD doses for groups A, B and C were r=0.51 (P=0.037), r=0.74 (P=0.0002) and r=0.96 (P=0.0001), respectively. Histopathological findings related to AD lung toxicity, such as interstitial pneumonitis and foamy alveolar macrophages, were observed more frequently in groups B and C than in group A. According to our findings, ^99mTc-HMPAO lung uptake is correlated with AD dose. ^99mTc-HMPAO lung imaging can demonstrate AD-induced lung injury.     

Correlation of Glut-1 glucose transporter expression with [18F]FDG uptake in non-small cell lung cancer

Positron emission tomography (PET) with [¹⁸F]2-fluoro-2-deoxy-D-glucose (FDG) may show negative results for bronchioloalveolar lung carcinoma. We investigated the correlation of Glut-1 glucose transporter expression with [¹⁸F]FDG uptake in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma) were studied. Final diagnoses were established by histology (via thoracotomy) in all patients. [¹⁸F]FDG PET was performed 40 min after i.v. injection of 185 MBq [¹⁸F]FDG. For semi-quantitative analysis of [¹⁸F]FDG uptake, standardized uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were negative for the expression of Glut-1, while only one (4.3%) of 23 non-bronchioloalveolar adenocarcinomas was negative (P<0.0001). The percentages of Glut-1-positive area, as well as the SUVs, were significantly lower in bronchioloalveolar carcinomas (n=7) (2.86%lj.56% and 1.25ǂ.75, respectively) than in non-bronchioloalveolar adenocarcinomas (n=23) (54.83%ᆭ.64%, P<0.0001, and 3.94ǃ.93, P=0.001, respectively). The degree of cell differentiation correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma of the lung. Correlations between SUVs and the intensity of Glut-1 immunoreactivity were also significant (intensities 0 and 1, n=11, SUV 1.47ǂ.63; intensities 2 and 3, n=23, SUV 4.78DŽ.13; P<0.0001). The percentage of Glut-1-positive area correlated significantly with SUVs (n=34, r=0.658, P<0.01). Overexpression of Glut-1 correlated with high [¹⁸F]FDG uptake. These findings suggest that Glut-1 expression is related to [¹⁸F]FDG uptake in non-small cell lung cancer. Glut-1 expression, as well as [¹⁸F]FDG uptake, correlated with the degree of cell differentiation in adenocarcinomas, and both Glut-1 expression and [¹⁸F]FDG uptake were significantly lower in bronchioloalveolar carcinomas than in non-bronchioloalveolar carcinomas.     

Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study

Gastrin-releasing peptide (GRP) receptor scintigraphy could allow prediction of response to GRP receptor-targeted treatment options, early non-invasive diagnosis and in vivo prognostic stratification of GRP receptor-positive tumours. This study reports on the imaging characteristics and efficacy for tumour detection of technetium-99m RP527, a ^99mTc chelated targeting peptide derived from bombesin, which binds GRP receptors with high affinity. Ten patients (four men and six women, mean age 56.4 years) either suffering from metastasised prostate (n, number of patients = 4) or breast carcinoma (n=1) or presenting with a clinical diagnosis highly suggestive for breast carcinoma (n=5) were included in the study. In the latter five patients, ^99mTc-RP527 scintigraphy was performed prior to diagnostic, e.g. biopsy, and staging examinations. Final diagnosis in these patients was breast carcinoma in all five. In all patients, whole-body planar scans and tomographic images were acquired 1 h and 5-6 h post injection of 555 MBq ^99mTc-RP527 and tumour to normal tissue (T/N) ratios determined. ^99mTc-RP527 showed specific uptake in four of six breast and one of four prostate carcinomas. T/N ratios derived from planar and tomographic images increased significantly (P<0.01) from 1.65 (SD 1.53) and 3.35 (SD 3.04) to 2.58 (SD 1.26) and 7.23 (SD 8.46), respectively. T/N ratios derived from tomographic images were consistently higher (P<0.01). The data presented suggest that ^99mTc-RP527 results in specific tumour localisation and exhibits good imaging characteristics with a good T/N ratio that may be further enhanced by single-photon emission tomography.     

89SrCl2在治疗乳腺癌骨转移中的临床疗效

目的 评价⁸⁹SrCl₂治疗乳腺癌骨转移的临床疗效,及其血液学毒副作用。方法 51例患者接受⁸⁹SrCl₂治疗,静脉注射剂量为2.22 MBq/kg体重,观察治疗前后止痛效果,病灶变化和外周血细胞变化。结果 患者疼痛完全缓解率为37.7%(17/45),总缓解率为84.4%。病灶治疗有效率为62.7%(32/51)。治疗后1个月白细胞和血小板减少者分别为76.5%和62.7%。3个月后大多数患者经治疗血象恢复到正常。结论 ⁸⁹SrCl₂可安全、有效地治疗乳腺癌骨转移患者的疼痛,并对其生活质量有所改善。     

99mTc-tetrofosmin SPET in the detection of both primary breast cancer and axillary lymph node metastasis

The aim of this study was to evaluate the usefulness of ^99mTc-tetrofosmin single-photon emission tomography (SPET) in the detection of both primary breast cancer and axillary lymph node metastasis. We studied 192 consecutive patients in whom primary breast cancer was suspected on the basis of mammography and/or physical examination. After intravenous injection of 740 MBq ^99mTc-tetrofosmin, both planar and SPET scintimammography was performed in all patients using a rectangular dual-head gamma camera equipped with low-energy, high-resolution, parallel-hole collimators. In 175 patients with breast cancer at histology, the per-lesion overall sensitivity of SPET and planar imaging for the detection of breast cancer was 95.8% and 75.9% (P<0.0005), respectively. The sensitivity of SPET and planar imaging was, respectively, 96.5% and 79.5% in palpable (P<0.0005) and 90% and 45% in non-palpable lesions (P<0.01). With regard to lesion size, the sensitivity of SPET and planar imaging was, respectively, 90.5% and 45.2% in lesions ⢪ mm (P<0.0005), 95.3% and 81.4% in lesions of 11-20 mm (P<0.005), 100% and 84.6% in lesions of 21-30 mm (P<0.05) and 100% and 95.8% in lesions >30 mm (P>0.05). In the remaining 17 patients with benign mammary lesions at histology, per-lesion overall specificity of SPET and planar imaging was 76.2% and 85.7% (P>0.05), respectively. Neither SPET nor planar imaging showed false-positive results in non-palpable lesions or in those ⢪ mm. In 173 breast cancer patients submitted to axillary lymph node dissection (ALND), per-axilla overall sensitivity of SPET and planar imaging in the detection of axillary lymph node metastasis was 93% and 52.3% (P<0.0005), respectively. The sensitivity of SPET and planar imaging was, respectively, 100% and 82.6% in palpable nodes (P>0.05), 90.5% and 41.3% in non-palpable nodes (P<0.0005), 92.8% and 35.7% in the presence of Г nodes (P<0.0005) and 93.2% and 68.2% in the presence of >3 nodes (P<0.005). The specificity of SPET and planar imaging was 91% and 100% (P<0.05), respectively. ^99mTc-tetrofosmin SPET appears to be a reliable method for the detection of both primary BC and axillary lymph node metastasis, and its diagnostic accuracy exceeds that of ^99mTc-tetrofosmin planar scintimammography. The use of SPET is particularly important in the identification of small non-palpable primary carcinomas and metastatic axillae with Г non-palpable lymph nodes. More extensive use of SPET appears warranted in the management of breast cancer patients.     

Improved response of colon cancer xenografts to radioimmunotherapy with pentoxifylline treatment

A methylxanthine, pentoxifylline (PTX), has the potential to improve tumour microcirculation and oxygenation in vivo. We aimed to determine whether this agent would enhance the response of tumours to experimental radioimmunotherapy (RIT). Balb/c nu/nu mice with xenografts of LS180 human colon cancer were treated with 4.63 MBq of ¹³¹I-A7 anti-colorectal monoclonal antibody. A dose of 50 mg/kg of PTX was administered i.p. immediately after the ¹³¹I-A7 injection and daily thereafter for 7 days. The effect of PTX administration on ¹³¹I-A7 targeting in tumours was assessed with biodistribution and radioluminography on day 2. Intratumoural pO₂ was measured with microelectrodes. The administration of PTX alone did not suppress tumour growth, but the efficacy of RIT with ¹³¹I-A7 was significantly improved by PTX: tumour volumes on day 15, relative to the initial volume, were 16.8Dž.60 in the non-treated controls, 13.9DŽ.17 with PTX, 3.43ǂ.44 with RIT, and 1.86ǂ.59 with RIT+PTX (P<0.05). PTX administration did not alter the biodistribution or intratumoural distribution of ¹³¹I-A7. However, intratumoural pO₂ was significantly improved by PTX administration: 16.9Nj.75 mmHg in control tumours versus 25.6ᆟ.3 mmHg in PTX-treated tumours (P<0.01). These results indicate that PTX-induced radiosensitisation of tumour cells due to better oxygenation is responsible for the better RIT outcomes, because the net radiation absorbed dose to the tumours did not appear to be changed.