A Review of Theranostics: Perspectives on Emerging Approaches and Clinical Advancements.

Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired radiopharmaceuticals to image and selectively treat various cancers. The clinical use of theranostics has increased in recent years, with U.S. Food and Drug Administration (FDA) approval of lutetium 177 (177Lu) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) and 177Lu-prostate-specific membrane antigen vector-based radionuclide therapies. The field of theranostics has imminent potential for emerging clinical applications. This article reviews critical areas of active clinical advancement in theranostics, including forthcoming clinical trials advancing FDA-approved and emerging radiopharmaceuticals, approaches to dosimetry calculations, imaging of different radionuclide therapies, expanded indications for currently used theranostic agents to treat a broader array of cancers, and emerging ideas in the field. Keywords: Molecular Imaging, Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, Molecular Imaging-Target Development, PET/CT, SPECT/CT, Radionuclide Therapy, Dosimetry, Oncology, Radiobiology © RSNA, 2023.

Stereotactic body radiotherapy in patients with adrenal gland metastases of oligometastatic and oliogoprogressive lung cancer.

Objective: To evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) in patients with adrenal gland metastasis (AGM) of oligometastatic lung cancer. Methods: Between June 2013 and May 2021, 44 patients with oligometastatic lung cancer (51 AGMs) were treated with SBRT. Forty-six (90%) lesions received a biological effective dose (BED10, α/ß = 10) of 100 Gy. The primary endpoint was local control (LC). Local control (LC), overall survival (OS), and progression-free survival (PFS) curves were calculated by the Kaplan-Meier method. Results: The median follow-up was 23 months. The most common histology was non-small cell lung cancer (88.6%). The 1- and 2-year LC rates were both 95% and 91%, respectively. Overall survival was better in patients with solitary AGMs in univariate analysis. Conclusion: This study demonstrated that SBRT with higher BED is associated with satisfactory LC and low toxicity rates in patients with AGM of oligometastatic lung cancer.

Role of gamma probe-assisted intraoperative sentinel lymph node evaluation in predicting axillary breast cancer metastasis after neoadjuvant chemotherapy.

OBJECTIVE: Intraoperative sentinel lymph node biopsy is a universally accepted technique to identify patients who are candidates for axillary lymph node dissection during breast cancer surgery. However, there is controversy over its use in patients who underwent preoperative neoadjuvant chemotherapy. This study aimed to examine the diagnostic value of gamma probe-assisted intraoperative sentinel lymph node examination with frozen section in breast cancer patients who had undergone preoperative neoadjuvant chemotherapy. METHODS: This retrospective study included 94 tumors diagnosed with stage IIA, IIB or IIIA invasive breast cancer with locoregional lymph node metastasis who underwent surgical treatment after neoadjuvant chemotherapy. Intraoperatively, axillary sentinel lymph node sampling was done using radioactive colloid and gamma probe and materials were examined with frozen section method. Patients with positive sentinel nodes underwent axillary resection. Histopathological examination of all surgical samples was done postoperatively. RESULTS: In 87 of 94 tumors (92.6%), a sentinel lymph node could be identified using the method. The sensitivity, specificity and accuracy of the method for predicting axillary macro metastasis were 85.7, 86.5 and 86.2%, respectively, with 5.7% false negative rate. CONCLUSIONS: Sentinel lymph node identification using preoperative scintigraphy and intraoperative use of gamma probe seems to be a feasible and efficient method in terms of differentiating patients that require axillary lymph node dissection during breast cancer surgery, even when they have received neoadjuvant chemotherapy. Further large prospective studies allowing subgroup analyses are warranted.

Re-Irradiation of Locoregional NSCLC Recurrence Using Robotic Stereotactic Body Radiotherapy.

BACKGROUND: We evaluated the efficacy, toxicity, and dose responses of re-irradiation with stereotactic body radiotherapy (SBRT) in patients with recurrent non- small cell lung cancer (NSCLC) after previous irradiation. PATIENTS AND METHODS: 28 patients were included. Previous median radiation doses were 54 and 66 Gy. The median interval time between previous radiotherapy and SBRT was 14 months. The median follow-up time after SBRT was 9 months (range 3-93 months). To evaluate the effectiveness of SBRT, local control, overall survival, and treatment-related toxicity were reported. RESULTS: SBRT doses and fractionation ranged from 60 to 30 Gy and from 3 to 8, respectively, according to previous doses, location of the recurrence, and interval time. 65% of tumor recurrences overlapped with previous treatment, while 35% of tumors recurred outside of the previous treatment. 4 patients had local progression after SBRT at their first follow-up. The Kaplan-Meier estimates of the 1- and 2-year actuarial overall survival were 71 and 42%, respectively. The mean survival following SBRT was 32.8 months, and the median survival was 21 months. No grade 3 or higher toxicities were observed. CONCLUSION: Robotic SBRT is a tolerable treatment option with manageable toxicity which can be used with radical or palliative intent in carefully selected patients with locally recurrent tumors after previous irradiation.

Use of Positron Emission Tomography/Computed Tomography in Radiation Treatment Planning for Lung Cancer.

Radiotherapy (RT) plays an important role in the treatment of lung cancer. Accurate diagnosis and staging are crucial in the delivery of RT with curative intent. Target miss can be prevented by accurate determination of tumor contours during RT planning. Currently, tumor contours are determined manually by computed tomography (CT) during RT planning. This method leads to differences in delineation of tumor volume between users. Given the change in RT tools and methods due to rapidly developing technology, it is now more significant to accurately delineate the tumor tissue. F18 fluorodeoxyglucose positron emission tomography/CT (F18 FDG PET/CT) has been established as an accurate method in correctly staging and detecting tumor dissemination in lung cancer. Since it provides both anatomic and biologic information, F18 FDG PET decreases inter-user variability in tumor delineation. For instance, tumor volumes may be decreased as atelectasis and malignant tissue can be more accurately differentiated, as well as better evaluation of benign and malignant lymph nodes given the difference in FDG uptake. Using F18 FDG PET/CT, the radiation dose can be escalated without serious adverse effects in lung cancer. In this study, we evaluated the contribution of F18 FDG PET/CT for RT planning in lung cancer.

Pathogens isolated from deep soft tissue and bone in patients with diabetic foot infections.

BACKGROUND: We sought to determine the similarity of pathogens isolated from soft tissue and bone in patients with diabetic foot infections. It is widely believed that soft-tissue cultures are adequate in the determination of causative bacteria in patients with diabetic foot osteomyelitis. The culture results of specimens taken concurrently from soft-tissue and bone infections show that the former does not predict the latter with sufficient reliability. We sought to determine the similarity of pathogens isolated from soft tissue and bone in patients with diabetic foot infections. METHODS: Forty-five patients with diabetic foot infections were enrolled in the study. Patients had to have clinically suspected foot lesions of grade 3 or higher on the Wagner classification system. In patients with clinically suspected osteomyelitis, magnetic resonance imaging, scintigraphy, or histopathologic examination were performed. Bone and deep soft tissue specimens were obtained from all patients by open surgical procedures under aseptic conditions during debridement or amputation. The specimens were compared only with the other specimens taken from the same patients. RESULTS: The results of bone and soft-tissue cultures were identical in 49% (n = 22) of cases. In 11% (n = 5) of cases there were no common pathogens. In 29% (n = 13) of cases there were more pathogens in the soft-tissue specimens; these microorganisms included microbes isolated from bone cultures. In four patients (9%) with culture-positive soft-tissue specimens, bone culture specimens remained sterile. In one patient (2%) with culture-positive bone specimen, soft-tissue specimen remained sterile. CONCLUSION: Culture specimens should be obtained from both the bone and the overlying deep soft tissue in patients with suspected osteomyelitis whose clinical conditions are suitable. The decision to administer antibiotic therapy should depend on these results.

The value of combined peritumoral and subdermal injection techniques for lymphoscintigraphy in detection of sentinel lymph node in breast cancer.

PURPOSE: The aim of this study was to evaluate the success rate of combined peritumoral and subdermal injection techniques based on our previous experience on different injection techniques for lymphoscintigraphy. PATIENTS AND METHODS: Fifty-nine women with early breast cancer (mean tumor size, 20.5 mm) were prospectively studied. On the morning of the operation, each patient had 2 injections, one peritumoral (PT) medial to the lesion and one subdermal (SD) into the skin over the tumor quadrant. Each injection consisted of 20 MBq (540 mCi) Tc-99m rhenium sulfide colloid. Early dynamic and delayed static images were obtained up to 4 hours after injections. An intraoperative gamma probe was used to explore the axillary sentinel lymph nodes (SLN). All surgical specimens were evaluated histopathologically. RESULTS: Forty patients had breast-preserving surgery and 19 had modified radical mastectomy. Thirty-eight patients had axillary dissection. All but 4 patients showed axillary lymphatic drainage. Twelve of 59 patients (20%) showed extraaxillary drainage with lymphoscintigraphy. Combined injection technique yielded a 93.2% success rate in detecting axillary SLN. In 2 of 4 patients with no drainage on lymphoscintigraphy, intraoperative gamma probe revealed SLN during the surgery. Twenty patients (33%) had positive axillary lymph nodes. In 14 of them, the SLN was the only positive node. A false-negative rate was found 1.6% (one of 59 patients). CONCLUSION: This results suggest that a combination of both PT and SD techniques increases the success rate of visualization SLN and enhances the visualization of extraaxillary nodes for further treatment planning.

Role of 99mTc-hexakis-2-methoxyisobutylisonitrile for detecting marrow metastases in childhood solid tumours.

AIM: To evaluate the role of 99mTc-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) for detecting bone marrow metastases in childhood solid tumours, including lymphomas. METHODS: Twenty-six children (18 males, eight females) were studied. They all had proven malignant solid tumours [Hodgkin's lymphoma (5), non-Hodgkin's lymphoma (3), neuroblastoma (9), Ewing's sarcoma (3), Langerhans cell histiocytosis (4), rhabdomyosarcoma (1) and germ cell tumour (1)] with suspected bone marrow metastases. All patients underwent computed tomography and/or magnetic resonance imaging, 99mTc-MIBI and Tc-methylene diphosphonate bone scans and bone marrow aspiration and/or biopsy. The scintigraphic evaluation of 99mTc-MIBI scans was performed according to the visual assessment of the extent and intensity of uptake. The scintigraphic score, which is the sum of the extent and intensity of uptake, was calculated for each patient. Scores of more than 2 were considered to be positive for bone marrow involvement. RESULTS: Twenty-seven 99mTc-MIBI scans were studied for 26 patients. Twenty-two 99mTc-MIBI scans were accepted as normal bone marrow. Bone scans were also normal in these patients. Five of the 27 99mTc-MIBI scans had scores of more than 2. Bone marrow cytology revealed bone marrow metastases in these patients. CONCLUSION: Abnormal 99mTc-MIBI uptake correlated extremely well with bone marrow aspiration/biopsy cytology results. Non-invasive 99mTc-MIBI imaging in children with malignant solid tumours appears to be promising for the evaluation of bone marrow metastases.