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Unlabelled: Previous reports have shown that axillary sentinel lymph node (ASLN) radiodetection allows accurate axillary staging for patients with early breast cancer. Radioguided surgery implies the use of a gamma-probe to count the emitted radioactivity of marked ASLNs. Several gamma-probes are commercially available, each with its own properties. The clinical impact of the type of gamma-probe used for ASLN radiodetection remains to be evaluated., Methods: Three commercially available gamma-probes were evaluated: a scintillator with a bismuth germanate crystal (probe A), a semiconductor with a cadmium telluride crystal (probe B), and a semiconductor with a cadmium zinc telluride crystal (probe C). Two hundred patients with early breast cancer were prospectively enrolled to undergo ASLN radiodetection and axillary lymphadenectomy. ASLN mapping consisted of injecting (99m)Tc-sulfur-colloid around the tumor. For each patient, sentinel lymph nodes were counted successively with the 3 probes and the sensitivity of each gamma-probe was determined from ASLN residual activity. The results of detection rates and false-negative rates for each probe were compared., Results: Mean residual ASLN activity was 52 kBq (range, 0.07-189 kBq). Sensitivity was compared among the 3 probes and found to be best for probe A. The detection rate of probe A was significantly better than that of probe B (93% vs. 86%, P = 0.05) but not different from that of probe C (93% vs. 90%). No differences in false-negative rates were observed among the 3 probes., Conclusion: ASLN detection rate depends on the type of gamma-probe used. Because failure to detect the ASLN leads to complete axillary lymphadenectomy, involving local morbidity and other sequelae, the type of gamma-probe must be considered important for sentinel lymph node radiodetection.

Unlabelled: The purpose of this study was to compare the toxicity and efficacy of two-step radioimmunotherapy using a bispecific anticarcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA) antibody (F6-734 bispecific monoclonal antibodies (BsMAbs) and an 131I-di-DTPA-TL bivalent hapten with F(ab')2 fragments of the same directly labeled anti-CEA 131-F6., Methods: Eight groups of nude mice subcutaneously grafted with the human TT medullary thyroid cancer cell line were injected once tumor volume reached about 200 mm3. Two groups received 37 or 92.5 MBq (1 or 2 nmol) 131I-di-DTPA-TL 48 h after injection of 2 or 4 nmol F6-734 BsMAb and two groups received 37 or 92.5 MBq (250 microg) 131I-F6. Four control groups were treated respectively with (a) 92.5 MBq nonspecific 131I-734 fragments, (b) 92.5 MBq 131I-di-DTPA-TL 48 h after injection of a mixture of irrelevant F6-679 (anti-CEA/anti-histamine) and G7A5-734 (anti-melanoma/anti-DTPA) BsMAb, (c) 250 microg nonradiolabeled F6, and 250 microg F6-734 BsMAb and then 48 h later 1.25 nmol of nonradiolabeled hapten. A control group received no injections. Toxicity was evaluated by determining animal weight and the number of leukocytes and platelets, and efficacy by variation in tumor volume and thyrocalcitonin during a 90-d period. Histological analysis of tumors and statistical studies were performed., Results: The time required for the tumor to double in size was respectively 57 and 86 d with 37 and 92.5 MBq F6-734/131I-di-DTPA-TL and 44 and 65 d with 37 and 92.5 MBq 131I-F6. Changes in thyrocalcitonin levels were parallel to those in tumor volume. Weight loss was 5%, leukocyte nadirs respectively 1640+/-838 and 1560+/-1160/mm3 and platelet nadirs 1.46+/-0.52 10(6)/mm3 and 0.73+/-0.38 10(6)/mm3 after injections of 37 and 92.5 MBq F6-734/1311-di-DTPA-TL. Weight loss was respectively 8% and 16%, leukocyte nadirs 50+/-100/mm3 and 175+/-50/mm3 and platelet nadirs 0.71+/-0.18 10(6)/mm3 and 0.48+/-0.11 10(6)/mm3 after injections of 37 and 92.5 MBq 131I-F6., Conclusion: Two-step radioimmunotherapy was as efficient as the one-step system and markedly less toxic.

Unlabelled: The purpose of this study was to evaluate biodistributions and absorbed doses of anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA)-indium (anti-DTPA-In) bispecific monoclonal antibody (BsMAb) F6-734 and 125I-labeled DTPA-indium dimer hapten (125I-di-DTPA-In hapten) in athymic mice xenografted with human medullary thyroid cancer., Methods: Bispecific monoclonal antibodies F6-679 (anti-CEA/antihistamine) and G7A5-734 (antimelanoma/anti-di-DTPA-In) were used as irrelevant BsMAbs. Athymic mice inoculated with TT medullary thyroid cancer cells expressing CEA were administered BsMAbs F6-734, F6-679 or G7A5-734 and then, 48 hr later, 125I-di-DTPA-In hapten. Iodine-125-labeled F6 F(ab')2 fragment was injected into other groups of mice. Biodistributions were examined at 30 min and 5, 24, 48 and 96 hr after injection of 125I-di-DTPA-In hapten or 125I-labeled F6 F(ab')2., Results: In mice injected with BsMAb F6-734 and 125I-di-DTPA-In hapten, tumor uptake was 9.1%+/-2.1%, 8.7%+/-3.5%, 8.0%+/-2.3%, 5.1%+/-0.9% and 3.5%+/-1.5% of the injected dose/g at 30 min and 5, 24, 48 and 96 hr, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 37.0+/-12.5, 32.3+/-10.9 and 10.4+/-2.7 at 24 hr. Iodine-125-F6 F(ab')2 fragment showed a tumor uptake of 7.39% injected dose/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 1.8+/-0.6, 7.3+/-2.9 and 3.6+/-1.6 at 24 hr. In mice injected with F6-679 or G7A5-734, tumor uptake and tumor-to-normal tissue ratios were much lower than in the mice injected with F6-734. These results were confirmed by autoradiographic studies that demonstrated clear tumor-to-normal tissue contrast., Conclusion: This two-step targeting method seems very potent for the diagnosis and therapy of human medullary thyroid cancer and other CEA-producing tumors because it combines high tumor uptake and low normal tissue background.

Unlabelled: The purpose of this study was to estimate the dose delivered to tumor targets and normal tissues after two-step injection of an anti-CEA/anti-DTPA-In (F6-734) bispecific antibody and a 131I-labeled di-DTPA in-TL bivalent hapten in patients with medullary thyroid carcinoma (MTC) and small-cell lung cancer (SCLC)., Methods: Five patients with persistent disease or recurrences of MTC and five patients with primary SCLC or relapse were studied. In a first step, 0.1 to 0.3 mg/kg of F6-734 bispecific antibody was injected intravenously. Four days later, 6 nmole (5.8 to 9.8 mCi) of 131I-labeled di-DTPA in-TL bivalent hapten were injected. Quantitative imaging was performed during one week after the second injection., Results: All 5 patients with MTC showed positive immunoscintigraphy (IS). In the smallest visualized and resected tumor (0.8 g), the fraction of injected activity per gram (% ID/g) was 0.1% at Day 3. IS was positive in 4 of the 5 patients with SCLC. The volume of the smallest visualized SCLC tumor was estimated at 11 +/- 2 ml, and tumor uptake was about 0.009% ID/g. Tumor dose estimates ranged from 4.2 to 174 cGy/mCi in patients with MTC and from 1.7 to 8 cGy/mCi in patients with SCLC., Conclusion: High absorbed dose values were calculated for small MTC recurrences. For SCLC recurrences the values were smaller but in the same range as those obtained by other investigators with the one-step technique in lymphoma.