After unsuccessful surgery, medullary thyroid carcinoma (MTC) may be fatal or remain stable for decades, and precise survival predictors are needed. This study assesses the prognostic value of calcitonin and carcinoembryonic antigen (CEA) doubling-times (DT). This is a retrospective study on 65 MTC patients from 2.9-29.5 yr after surgery. Data registered in the database of the French Neuroendocrine Tumor Group were analyzed anonymously. All patients had abnormal calcitonin levels after total thyroidectomy and bilateral lymph node dissection. Calcitonin and CEA serum levels were measured during routine disease follow-up. To assess DT as prognostic factors, a patient population was extracted from the database. When calcitonin DT was less than 6 months, 5- and 10-yr survivals were three of 12 (25%) and one of 12 (8%), respectively; when between 6 months and 2 yr, 5- and 10-yr survivals were 11 of 12 (92%) and three of eight (37%), whereas all 41 patients with calcitonin DT greater than 2 yr were alive at the end of the study. Tumor-Node-Metastasis (TNM) stage, European Organization for Research and Treatment of Cancer (EORTC) score, and calcitonin DT were significant predictors of survival by univariate analysis, but only calcitonin DT remained an independent predictor of survival by multivariate analysis (P = 0.002) with a proportion of variance explained (PVE) of 37.4%. Calcitonin DT was a better predictor than CEA (PVE 63.3% and 47.0%, respectively). Calcitonin DT calculated using only the first four measurements was also an independent predictor of survival (P < 0.000001; PVE 40.4%). Calcitonin DT may be superior to initial clinical staging and among the most powerful prognostic indicators in MTC.

This article reviews the methods of pretargeting, which involve separating the targeting antibody from the subsequent delivery of an imaging or therapeutic agent that binds to the tumor-localized antibody. This provides enhanced tumor:background ratios and the delivery of a higher therapeutic dose than when antibodies are directly conjugated with radionuclides, as currently practiced in cancer radioimmunotherapy. We describe initial promising clinical results using streptavidin-antibody constructs with biotin-radionuclide conjugates in the treatment of patients with malignant gliomas, and of bispecific antibodies with hapten-radionuclides in the therapy of tumors expressing carcinoembryonic antigen, such as medullary thyroid and small-cell lung cancers.

Purpose: No effective therapy is currently available for the management of patients with metastatic medullary thyroid carcinoma (MTC). The efficacy of pretargeted radioimmunotherapy (pRAIT) with bispecific monoclonal antibody (BsMAb) and a iodine-131 (¹³¹I) –labeled bivalent hapten is evaluated. Patients and Methods: Twenty-nine patients with advanced, progressive MTC, as documented by short serum calcitonin doubling times (Ct DTs), received an anti–carcinoembryonic antigen (CEA)/anti–diethylenetriamine pentaacetic acid (DTPA) –indium BsMAb, followed 4 days later by a ¹³¹I-labeled bivalent hapten. Overall survival (OS) was compared with 39 contemporaneous untreated MTC patients with comparable prognostic indicators. Results: OS was significantly longer in high-risk, treated patients (Ct DT < 2 years) than in high-risk, untreated patients (median OS, 110 v 61 months; P < .030). Forty-seven percent of patients, defined as biologic responders by a more than 100% increase in CtDT, experienced significantly longer survival than nonresponders (median OS, 159 v 109 months; P < .035) and untreated patients (median OS, 159 v 61 months; P < .010). Treated patients with bone/bone-marrow disease had a longer survival than patients without such involvement (10-year OS, 83% v 14%; P < .023). Toxicity was mainly hematologic and related to bone/bone-marrow tumor spread. Conclusion: pRAIT against CEA induced long-term disease stabilization and a significantly longer survival in high-risk patients with Ct DTs less than 2 years, compared with similarly high-risk, untreated patients. Ct DT and bone-marrow involvement appear to be prognostic indicators in MTC patients who undergo pRAIT.

As a first step in the synthesis and the study of DNA polyintercalating drugs, dimers of acridines have been prepared. Their DNA binding properties have been studied. It has been determined that when the chain separating the two aromatic rings is longer than a criticål distance, bisintercalation is actually observed and that the DNA binding affinity becomes quite large (greater than 10(8)-10(9) M-1). It is shown also that the optical characteristics of these molecules are dependent on the sequences of DNA. The fluorescence intensity of one of these dimers when bound to DNA varies as the fourth power of its A+T content. This derivative could be used as a fluorescent probe of DNA sequence.