Faculty Bibliography

Sequential Tc-99m hydroxymethylene-diphosphonate (HDP) 3-phase bone (BS) and In-111 leukocyte scanning (WBCS) have been frequently used to evaluate the diabetic foot, as nonosteomyelitis BS uptake is repeatedly observed and osteomyelitis (OM) in WBCS is often uncertain without BS correlation. Additionally, both modalities are limited in lesion localization because of low resolution and lack of anatomic details. We investigated a method that combined BS/WBCS, and if needed, WBCS/bone marrow scanning (BMS) using SPECT/CT to accurately diagnose/localize infection in a practical protocol. Blood flow/pool images were obtained followed by WBC reinjection and next day dual isotope (DI) BS/WBCS planar and SPECT/CT. BMS/WBCS SPECT/CT (step 2 DI) was obtained on the following day when images were suspicious for mid/hindfoot OM. Diagnosis accuracy and confidence were judged for the various imaging combinations. Diagnosis was classified as OM, soft tissue infection (STI), both OM/STI, and other/no bony pathology by microbiology/pathology or follow-up. Distinction between various diagnostic categories and overall OM diagnostic accuracy in 213 patients were higher for DI than WBCS or BS alone, and for DI SPECT/CT than DI planar or SPECT only. Diagnostic confidence/lesion site was significantly higher for DI SPECT/CT than other comparative imaging methods. In a group of 97 patients with confirmed microbiologic/pathologic diagnosis, similar results were attained. Step 2 DI SPECT/CT performed in 67 patients further improved diagnostic accuracy/confidence. DI SPECT/CT is a highly accurate modality that considerably improves detection and discrimination of STI and OM while providing precise anatomic localization in the diabetic foot. This combined imaging technique promises to beneficially impact diabetic patient care.

Schneiderian papillomas are benign tumors of the nasal cavity and paranasal sinuses often asymptomatic in their early stages. We report a case of a maxillary sinus oncocytic schneiderian papilloma first detected by positron-emission tomography by using fluorodeoxyglucose (FDG). Schneiderian papillomas demonstrate increased FDG uptake, similar to that of other oncocytic tumors, making it important for otolaryngologists and radiologists to realize that high uptake of FDG does not necessarily indicate a malignant lesion.

In this article, the discussions about concepts involved in anticancer therapy, including cell death pathways and the variables that guide clinical management, such as intents and types of anticancer therapy regimens and modalities, are a prelude to the review of FDG PET/CT imaging parameters used in the evaluation of response to therapy. The review also includes brief discussions about differences between evaluation of cytostatic and cytotoxic therapy regimens and induction and neoadjuvant therapy regimens.

This article discusses evaluating response after and during therapy in various settings and for the types of cancers for which ample evidence demonstrates that PET imaging with flourodeoxyglucose provides a valuable surrogate for response to therapy. It also briefly discusses pitfalls in obtaining an optimal assessment of response and issues that need further attention for this modality to become established as an independent predictor of response to anticancer therapy.

FDG PET/CT, an established imaging modality for staging and restaging workup of malignancies, also demonstrates increased uptake in infectious or inflammatory conditions, including both infectious and noninfectious granulomatous processes. A 65-year-old man with a history of hepatocellular carcinoma status post-wedge resection and chemoembolization of the primary tumor referred for evaluation of extrahepatic metastases for determining the surgical eligibility for a liver transplantation. The patient underwent FDG PET/CT imaging associated with a separately acquired contrast enhanced CT (CECT) of the chest, abdomen, and pelvis. FDG PET/CT imaging revealed multiple FDG-avid pulmonary nodules that were subsequently confirmed to represent Mycobacterium avium intracellular infection on histology.

PURPOSE/OBJECTIVE:To develop guidelines for performing and interpreting positron emission tomography (PET) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials. METHODS:An International Harmonization Project (IHP) was convened to discuss standardization of clinical trial parameters in lymphoma. An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma. Only recommendations subsequently endorsed by all IHP subcommittees were adopted. RECOMMENDATIONS/CONCLUSIONS:PET after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy. Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter, regardless of its location. A smaller residual mass or a normal sized lymph node (ie, < or = 1 x 1 cm in diameter) should be considered positive if its activity is above that of the surrounding background. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow are also proposed. Use of attenuation-corrected PET is strongly encouraged. Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospective registry.

PURPOSE/OBJECTIVE:Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response. PATIENTS AND METHODS/METHODS:Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues. RESULTS:Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment. CONCLUSION/CONCLUSIONS:Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

Radioimmunotherapy (RIT) with tositumomab and iodine 131 tositumomab can produce durable and complete responses in relapsed/refractory low-grade Non-Hodgkin's lymphoma. Patients with bone marrow involvement (BMI) with tumor >25% of the intertrabecular space are generally excluded from RIT because of risk of excessive hematologic toxicity. The authors conducted a dose-escalation study of tositumomab and iodine 131 tositumomab to determine whether RIT is feasible in this population. Patients had baseline BMI of >25% and platelet count of >or=150,000/mm3. In contrast to the usual 75 cGy total body dose of radiation, dose escalation of Iodine I 131 tositumomab began at a total body dose of 45 cGy, and increased to 55 cGy in a second cohort. Dose-limiting toxicity (DLT) was defined as absolute neutrophil count <500 cells/mm3 or platelets <25,000/mm3 for >17 days, or absolute neutrophil count <750/mm3 or platelets <50,000/mm3 for >24 days. Eleven subjects were enrolled (8 at 45 cGy and 3 at 55 cGy). Estimated BMI ranged from 30 to 65% (median approximately 40%). Patients had received a median of three prior chemotherapies (range 1 - 6). One of the six evaluable patients treated at 45 cGy experienced DLT. Three patients received 55 cGy, one had hematologic DLT concurrent with lymphoma progression and extensive BMI at relapse. Three of 11 (27%) patients received hematologic supportive care. Two patients had objective responses of 1 and 42.4+ months, respectively. RIT with attenuated dose iodine 131 tositumomab for patients with >25% BMI has acceptable toxicity and can result in lymphoma responses.