Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients.

AIM: The study evaluates the therapeutic efficacy of Strontium-89-chloride (89Sr) and 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) in the palliation of painful bone metastases from breast cancer. PATIENTS AND METHODS: Fifty patients with painful multifocal bone metastases from breast cancer entered the study and were randomized into two groups according to the radiopharmaceutical used: 148 MBq 89Sr i.v. (Group A: 25 patients) and 1406 MBq 186Re-HEDP i.v. (Group B: 25 patients). Pain palliation was evaluated on the basis of the Wisconsin pain test improvement at two months and response was graded as complete, partial, minimal or absent. Hematological toxicity and side effects were reported according to WHO guidelines. RESULTS: The global response rate was 84% (21/25) for 89Sr and 92% (23/25) for 186Re-HEDP, respectively. The onset of pain palliation appeared significantly earlier in Group B (p < 0.0001). The duration of pain relief ranged from two months to 14 months (mean of 125 days with a median value of 120 days) in Group A and from one month to 12 months (mean of 107 days with a median value of 60 days) in Group B (p = 0.39). A moderate hematological toxicity was apparent in both groups. Platelet and white blood cell counts returned to baseline levels within 12 weeks after 89Sr administration and 6 weeks after 186Re-HEDP administration (p < 0.01). CONCLUSIONS: Both 89Sr and 186Re-HEDP are effective and safe in bone pain palliation in breast cancer with the latter showing a significantly faster onset of pain relief.

99mTc-MIBI scintimammography using a dedicated nuclear mammograph.

UNLABELLED: This study reports on a prototype single-photon emission mammograph (SPEM) dedicated to 99mTc-hexakis-2-methoxyisobutile isonitrile (MIBI) scintimammography. Main technical features are reported together with physical performance. Preliminary patient data are also reported. METHODS: The SPEM detector head is composed of a CsI(T1) scintillating array coupled to a Hamamatsu R3292 position-sensitive photomultiplier tube with crossed-wire anode. The high-resolution collimator is 35-mm thick with a 1.7-mm hole diameter and a 0.2-mm septal thickness. The electronic acquisition system is composed of five integrated cards with computation based on high-speed programmable microprocessors. The readout electronics include correction maps for on-line energy correction and spatial uniformity. The small size of the detector head allows the use of mechanical breast compression to minimize detection distance and tissue scatter. After physical SPEM performance evaluation in vivo scintimammography was performed in 29 patients and was compared with a state-of-the-art Anger camera. RESULTS: The SPEM showed an intrinsic spatial resolution of 2 mm, an energy resolution of 23% FWHM at 122 keV and spatial uniformities of 18% (integral) and 13.5% (differential). The SPEM imaged one 0.4-cm carcinoma missed by the Anger camera and resolved as separate lumps an irregular focal uptake on the Anger camera image. The remaining cases yielded concordant results. CONCLUSION: The SPEM prototype presented in this study shows adequate physical characteristics for 99mTc-MIBI scintimammography.

99Tcm-MIBI scintimammography in 300 consecutive patients: factors that may affect accuracy.

We evaluated the diagnostic yield of 99Tcm-MIBI scintimammography in a relatively large series of consecutive patients referred for breast surgery on the basis of physical examination or mammogram. 99Tcm-MIBI uptake was correlated to tumour size, receptor status, neovascularity, proliferating activity, P-170 glycoprotein expression and the patient's gonadal state. Three hundred consecutive patients referred to our institution, with either a positive mammogram or a palpable mass, were entered into the study. All patients underwent 99Tcm-MIBI scintimammography. Pathological status was obtained after surgery in all patients. Breast cancer was diagnosed in 218 (73%) patients. The MIBI scan was positive in 89% (194/218) cancer patients and in 17% (14/82) of patients with benign masses (false-positives); the scan was negative in 24 (11%) cancer patients (false-negatives). The sensitivity of MIBI scintigraphy was higher for tumours > 1 cm (95 vs 48% in lesions < or = 1 cm) and in pre-menopausal women (95 vs 85%). Conversely, the specificity was better for lesions < 1 cm (100%) and in post-menopausal women (89%). The positive predictive value of MIBI scan was good both in small (< 1 cm) and large tumours (100% and 93%, respectively) and slightly modified by gonadal state (89% and 96% in pre- and post-menopausal state). The negative predictive value was unsatisfactory, especially in small tumours and in older patients. The diagnostic performance increased stratifying data for tumour size, indicating that lesion size is a major determinant in the diagnostic accuracy of MIBI scintimammography. We conclude that 99Tcm-MIBI scintimammography is useful in the diagnostic evaluation of young patients, because it can select patients for further invasive diagnostic procedures. In older patients, a positive 99Tcm-MIBI scan is highly suggestive of malignancy and might be an indication for surgery. In the case of a negative scan, biopsy is advisable given the poor negative predictive value. Small tumour size and a well-differentiated histotype characterize false-negative cases.

Platinum compounds as radiosensitizers in strontium-89 metabolic radiotherapy.

PURPOSE: Strontium-89 is currently used for the treatment of painful bone metastases. This study reports on two preliminary experiences with low-dose platinum compounds, carboplatin and cisplatin, as radiosensitizers in 89Sr therapy. PATIENTS AND METHODS: 30 patients entered the carboplatin study: 15 patients (Group A) were treated with 148 MBq 89Sr followed by carboplatin (100 mg/m2 at 7 and 21 days) and 15 patients (Group B) were treated with 89Sr alone. 12 patients entered the cisplatin study: six patients (Arm 1) received 148 Mq 89Sr plus cisplatin (50 mg/m2) in two administrations (immediately before and 10 days after 89Sr injection) and six patients (Arm 2) received 89Sr plus two placebo administrations. Pain response was assessed 8 weeks after the therapy on the Wisconsin score modifications. RESULTS: No clinically significant adverse effects or myelosuppression by platinum compounds were observed. In carboplatin study a pain response was observed in 20 of 27 (74%) evaluable patients, 13/15 in group A and 7/12 in group B. The pain response in the patients treated with 89Sr and carboplatin was clearly superior to that seen in the patients treated with 89Sr alone (P = 0.025), whereas survival was only marginally better in the combined treatment group (8.1 vs 5.7 months, P = 0.19). In cisplatin study a pain response was observed in 10 of 12 (83%) evaluable patients, 5/6 in Arm 1 and 4/6 in Arm 2. CONCLUSIONS: Low-dose platinum compounds seem to enhance the effects of 89Sr radioisotope therapy on pain from bone metastases without relevant hematological toxicity.

Technetium-99m-MIBI scintigraphy in the assessment of neoadjuvant chemotherapy in breast carcinoma.

UNLABELLED: Presurgical neoadjuvant chemotherapy (PSNC) is the treatment of choice for patients with locally advanced breast carcinoma (LABC). Accurate assessment of tumor response is important in planning subsequent treatments. Conventional response assessment by mammography and clinical evaluation is not fully reliable. This study evaluates the diagnostic yield of serial 99mTc-MIBI scintigraphy in the assessment of LABC response to PSNC. METHODS: Twenty-nine patients affected by LABC underwent clinical, mammographic and 99mTc-MIBI scintigraphy before and after 3 cycles of FEC (500 mg/m2 5-fluorouracil, 50 mg/m2 epirubicin and 400 mg/m2 cyclophosphamide) on Days 1 and 8. Surgery was planned for 15 days after the third cycle of chemotherapy. Pathological status was obtained after surgery in all patients. RESULTS: Sensitivities (i.e., true-positive ratios) for a correct prediction of tumor presence after PSNC were 65% for scintigraphy, 35% for clinical evaluation and 69% for mammography. Specificities (i.e., true-negative ratios) for a correct prediction of tumor absence after PSNC were 100% for scintigraphy, 67% for clinical evaluation and 33% for mammography. Technetium-99m-MIBI uptake in this series did not correlate with P-170 expression, proliferating cell nuclear antigen, Her-2/neu oncogene protein, antihuman endothelial cell CD31 antigen and estrogenic and progestinic receptor status. CONCLUSION: Technetium-99m-MIBI scintigraphy is effective in monitoring the response to PSNC in LABC patients. Its diagnostic yield is clearly superior to clinical evaluation alone. Scintigraphy performs as does mammography in patients with negative response, but it is clearly superior in patients with positive response.

Clinical relevance of 111In-octreotide scans in CNS tumors.

Sixty-six patients with a clinical and neuroradiological diagnosis of CNS tumors were evaluated by 111In-octreotide scintigraphy. Planar images were acquired at 2-4 and 24 hours after the injection of 111-185 MBq of 111In-octreotide (Octreoscan, Byk-Gulden). In the positive scans the tumor/non-tumor ratio was evaluated using a standard ROI method, and an uptake index (U.I.) of the lesion was determined. In vitro binding assays were performed on frozen sections from surgical specimens from 17 patients. All 32 meningiomas demonstrated a positive 111In-octreotide scan with a high U.I. Only 13 of 21 gliomas showed a positive scan, but the U.I. was significantly lower (p < 0.001 by "t"-test); one lymphoma showed a faint tracer uptake. All the other histotypes evaluated yielded negative scans. In all cases the receptorial pattern shown by the immunohistochemical staining technique was concordant with the scintigraphic results. 111In-octreotide scintigraphy allowed a differential diagnosis of meningioma versus other CNS tumors in 6 patients (4 neurinomas, 1 brain metastasis of melanoma, 1 lymphoma). In conclusion, 111In-octreotide scintigraphy is a promising tool to evaluate the SS receptorial pattern of CNS tumors and to increase the diagnostic specificity of conventional imaging providing useful information in selected cases for the therapeutic strategy.

111In-octreotide scintigraphy in small cell lung cancer.

Somatostatin receptors have been identified on the cellular surface of a subset of patients with small cell lung cancer (SCLC) and may be associated with a less aggressive evolution of the tumor. Moreover, medical therapy with somatostatin analogues holds promise for neoplastic growth control. We performed planar imaging in 22 patients with histologically proven SCLC at 2-4 and 24 hours after the injection of 111-185 MBq of 111In-DTPA-octreotide (Octreoscan, Byk-Gulden). Tumor uptake was observed in 19 patients in both early and late scans, while 2 patients previously treated with chemotherapy showed negative early and late scans. One patient had a positive early scan and a negative late scan. All the scintigraphic studies showed more extensive disease than expected by CT. No significant modification in tumor uptake of radiooctreotide was observed in three patients studied before and after chemotherapy. In conclusion, 111In-octreotide is a suitable radiopharmaceutical for the in vivo evaluation of the somatostatin receptors of small lung cancer. The prognostic and therapeutical implications of this nuclear technique must be further investigated, however.

Somatostatin receptor imaging in small cell lung cancer using 111In-DTPA-octreotide: a preliminary study.

Small cell lung cancer is a common and aggressive disease. Combined multiagent chemotherapy and radiotherapy can improve short-term prognosis, but long-term prognosis remains dim. Somatostatin receptors have been identified on the cellular surface of subsets of this cancer and may be associated with less aggressive evolution. Moreover, medical therapy with somatostatin analogues holds promise for neoplastic growth control. Planar scintigraphy has been performed in 15 patients with histologically proven small cell lung cancer at 4 and 24 h after the intravenous (i.v.) injection of 185 MBq 111In-octreotide (Octreoscan, BYK-Gulden). No short-term adverse effects were recorded; tumour uptake of the radiopharmaceutical was observed in 13 patients at 4 h and in 12 patients at 24 h suggesting more extensive disease than apparent by computed tomography (CT). It is highly likely that the 24 h uptake reflects the presence of somatostatin receptors on the tumour. Previous chemotherapy does not seem to play a key role in tumour visualization. 111In-octreotide is a suitable radiopharmaceutical for in vivo evaluation of somatostatin receptor status of small cell lung cancer. Quantitative scintigraphic methods are needed to investigate nonspecific binding and receptor kinetics.