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Additional file 1.

A case of primary thyroid lymphoma demonstrating uptake of 99mTc-hexakis-2-methoxy isobutyl isonitrile (MIBI) is presented. The 99mTc-MIBI image more clearly delineated the extent of tumor as demonstrated on CT compared to 201Tl-chloride and [99mTc]pertechnetate images. Following two courses of chemotherapy, repeat radionuclide studies and CT scan showed complete resolution of the thyroid tumor. Technetium-99m-MIBI may be useful in the assessment of disease activity and monitoring response to treatment in patients with lymphoma.

CC49 is a murine monoclonal antibody (MAb) that reacts against the TAG-72 antigen. We carried out a Phase I study with escalating doses of 131I-CC49 in patients with advanced colorectal cancer expressing the TAG-72 antigen to determine the dose-limiting toxicity and therapeutic efficacy, if any, of the radioimmunoconjugate.Twenty-four patients with TAG-72- expressing colorectal cancer were treated with escalating doses of 131I-CC49 starting at 15 mCi/m2 and going up to 90 mCi/m2 of 131I labeled to 20 mg MAb CC49. Patients were selected if TAG-72 was expressed inor = 50% of cells in previously resected tumor and at least one metastasis was demonstratable on standard imaging such as CT. All patients had failed conventional chemotherapy and had not received prior radiotherapy or murine MAb. Patients were under radiation isolation precautions until whole-body radioactivity decreased toor = 5 mR/hr at 1 m. Whole-body scintigrams were obtained prior to discharge and 1 and 2 wk after infusion in all patients. SPECT imaging was carried out at least once in all patients.All patients had excellent targeting of radioactivity to known tumor sites. There was no nonhematologic toxicity. Hematologic toxicity was more pronounced in those patients who had received extensive prior chemotherapy. There were no major responses. All patients developed an immune response (HAMA) within 4 wk of therapy.Radioimmunotherapy with 131I-CC49 is safe and there is significant therapeutic efficacy in this Phase I trial at the doses studied. There is excellent targeting of radioactivity to antigen-positive tumors. Dose-limiting toxicity is hematopoietic, with the maximum tolerated dose in this group of heavily pretreated patients being 75 mCi/m2.

Interim 18F-fluorodeoxyglucose positron emission tomography (Interim- 18F-FDG-PET,hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-celllymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determinethe optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL.Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (DSUVmax ). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects oftiming and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using DSUVmax , respectively. DSUVmax identified a larger proportion of poor respondersthan DS5 did. For all criteria, the negative predictive value was >80%, and positivepredictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs,2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOPtherapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Goodresponse at I-PET2 is suggested for de-escalation trials, and poor response using DSUVmax atI-PET4 is suggested for randomized trials that are evaluating new therapies