Unconventional non-amino acidic PET radiotracers for molecular imaging in gliomas.

PURPOSE: The objective of this review was to explore the potential clinical application of unconventional non-amino acid PET radiopharmaceuticals in patients with gliomas. METHODS: A comprehensive search strategy was used based on SCOPUS and PubMed databases using the following string: ("perfusion" OR "angiogenesis" OR "hypoxia" OR "neuroinflammation" OR proliferation OR invasiveness) AND ("brain tumor" OR "glioma") AND ("Positron Emission Tomography" OR PET). From all studies published in English, the most relevant articles were selected for this review, evaluating the mostly used PET radiopharmaceuticals in research centers, beyond amino acid radiotracers and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), for the assessment of different biological features, such as perfusion, angiogenesis, hypoxia, neuroinflammation, cell proliferation, tumor invasiveness, and other biological characteristics in patients with glioma. RESULTS: At present, the use of non-amino acid PET radiopharmaceuticals specifically designed to assess perfusion, angiogenesis, hypoxia, neuroinflammation, cell proliferation, tumor invasiveness, and other biological features in glioma is still limited. CONCLUSION: The use of investigational PET radiopharmaceuticals should be further explored considering their promising potential and studies specifically designed to validate these preliminary findings are needed. In the clinical scenario, advancements in the development of new PET radiopharmaceuticals and new imaging technologies (e.g., PET/MR and the application of the artificial intelligence to medical images) might contribute to improve the clinical translation of these novel radiotracers in the assessment of gliomas.

Serial scanning with 99mTc-3, 3-diphosphono-1, 2-propanodicarboxylic acid (99mTc-DPD) for early detection of cardiac amyloid deposition and prediction of clinical worsening in subjects carrying a transthyretin gene mutation.

BACKGROUND: To determine the capability of 99mTc-DPD scintigraphy to detect early cardiac involvement and predict clinical worsening in transthyretin (TTR) gene mutation patients. METHODS: Eleven mutated subjects with normal interventricular septum (IVS) thickness, NT-proBNP level and no cardiac symptoms underwent three seriate 99mTc-DPD scans (visually and semiquantitatively analyzed), and was followed-up for 5-8-years. RESULTS: Six patients showed no myocardial accumulation in all scans. Increased IVS thickness occurring in one patient 4 years after the last scan was the only abnormal finding in these patients; no cardiac symptoms developed during the follow-up. In three patients, cardiac radiotracer uptake was found at enrollment; other laboratory/instrumental abnormal findings occurred later and cardiac symptoms developed during the follow-up period. Two patients had a negative 99mTc-DPD scan at enrollment and showed cardiac uptake in the following scans. Increased mean left-ventricular (LV) wall thickness was found 3 years after positive scintigraphy; NT-proBNP increased later in one patient. These patients developed cardiac symptoms during the follow-up period. CONCLUSIONS: 99mTc-DPD scan detects cardiac involvement in subjects with TTR gene mutation earlier than ECG, echocardiography and biochemical markers, occurring some years before the fulfillment of current diagnostic criteria for cardiac amyloidosis. A positive 99mTc-DPD scan predicts cardiac symptoms onset.

Peptide receptor radionuclide therapy for aggressive pituitary tumors: a monocentric experience.

In aggressive pituitary tumors (PT) showing local invasion or growth/recurrence despite multimodal conventional treatment, temozolomide (TMZ) is considered a further therapeutic option, while little data are available on peptide receptor radionuclide therapy (PRRT). We analyzed PRRT effectiveness, safety and long-term outcome in three patients with aggressive PT, also reviewing the current literature. Patient #1 (F, giant prolactinoma) received five cycles (total dose 37 GBq) of 111In-DTPA-octreotide over 23 months, after unsuccessful surgery and long-term dopamine-agonist treatment. Patient #2 (M, giant prolactinoma) underwent two cycles (12.6 GBq) of 177Lu-DOTATOC after multiple surgeries, radiosurgery and TMZ. In patient #3 (F, non-functioning PT), five cycles (29.8 GBq) of 177Lu-DOTATOC followed five surgeries, radiotherapy and TMZ. Eleven more cases of PRRT-treated aggressive PT emerged from literature. Patient #1 showed tumor shrinkage and visual/neurological amelioration over 8-year follow-up, while the other PTs continued to grow causing blindness and neuro-cognitive disorders (patient #2) or monolateral amaurosis (patient #3). No adverse effects were reported. Including the patients from literature, 4/13 presented tumor shrinkage and clinical/biochemical improvement after PRRT. Response did not correlate with patients' gender or age, neither with used radionuclide/peptide, but PRRT failure was significantly associated with previous TMZ treatment. Overall, adverse effects occurred only in two patients. PRRT was successful in 1/3 of patients with aggressive PT, and in 4/5 of those not previously treated with TMZ, representing a safe option after unsuccessful multimodal treatment. However, at present, considering the few data, PRRT should be considered only in an experimental setting.

Differentiating malignant from benign thyroid nodules with indeterminate cytology by 99mTc-MIBI scan: a new quantitative method for improving diagnostic accuracy.

Quantitative 99mTc-MIBI thyroid scintigraphy is a useful tool in differentiating malignant from benign thyroid nodules with indeterminate cytology. The aim of our report is to compare the diagnostic performance of different quantitative methods. We prospectively evaluated 20 patients affected by a thyroid nodule with a cytological diagnosis of class III or IV according to the Bethesda system. Planar images of the thyroid were acquired 10 and 60 minutes after 99mTc-MIBI administration and two different quantitative methods applied (i.e. wash-out index, WOind; retention index, R.I.). All patients underwent lobectomy or thyroidectomy and final histological findings were matched with MIBI results obtained with both quantitative methods. Four out of 20 patients had a final histological result of differentiated thyroid cancer, while benign findings were found in the remaining cases. Overall sensitivity, specificity, accuracy, PPV and NPV were 100% in all for the WOind and 100%, 57.1%, 62.5%, 25% for the R.I., respectively. In conclusion 99mTc-semiquantitative MIBI thyroid scintigraphy with WOind calculation is highly accurate in differential diagnosis of nodules with indeterminate cytology reading.