The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...最新文献

Background: Maximum standardized uptake value (SUVmax) is the primary quantitave parameter given in 18F-FDG PET/CT reports. Calculations derived from three dimensional metabolic volumetric images have been proposed to be more successful than SUVmax alone in prognostification with a lower interobserver variability in many cancers. We aimed to determine the prognostic value of metabolic parameters derived from 18F-FDG PET/CT studies in small cell lung cancer (SCLC) patient population with a long follow-up time.

Methods: In this study, 38 consecutive SCLC patients (34M, 4F, age:65.76 ±8.18 years) who were referred to 18F-FDG PET/CT for staging between October 2006-January 2011 were included. SUVmax, SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. Overall survival (OS) was calculated from the date of the initial PET/CT to death from any cause. Survival tables were obtained and Kaplan Meier curves were reconstructed. Mantel-Cox regression analysis was performed in order to investigate if any of these parameters have an effect on survival along with other clinical risk factors.

Results: Median SUVmax, SUVmean, SUVpeak, MTV, TLG and LDH values were calculated as 13.9 g/dL, 6.4 g/dL,10.69 g/dL, 147 cm³, 1898.52 and 375U/L respectively. Median follow-up was 761.23±873.21 days (25.37 months, range:110-3338 days). Since basal 18F-FDG PET/CT scans, all patients were lost in the follow-up except for two patients. MTV was a significant prognostic factor in SCLC patients. Estimated mean survival times were 261.0±45.6 (95% CI: 171.6-350.3) days in patients with MTV value above the calculated median 147, and 577.0±124.0 (95% CI: 333.7-820.2) days in patients with MTV<147. The difference was statistically significant with a P=0.037.

Conclusions: Baseline whole body MTV reflecting total tumor load is a prognostic index in SCLC. SUV is insufficient to predict prognosis.

Background: Accurate identification and discrimination of post treatment changes from recurrent disease remains a challenge for patients with intracranial malignancies despite advances in molecular and magnetic resonance imaging. We have explored the ability of readily available Rubidium-82 chloride (⁸²RbCl) positron emission tomography (PET) to identify and distinguish progressive intracranial disease from radiation necrosis in patients previously treated with radiation therapy.

Methods: Six patients with a total of 9 lesions of either primary (N.=3) or metastatic (N.=6) intracranial malignancies previously treated with stereotactic radiation surgery (SRS) and persistent contrast enhancement on MRI underwent brain ⁸²RbCl PET imaging. Two patients with arteriovenous malformations previously treated with SRS, also had brain ⁸²RbCl PET imaging for a total of 11 lesions studied. Histological confirmation via stereotactic biopsy/excisional resection was obtained for 9 lesions with the remaining 2 classified as either recurrent tumor or radiation necrosis based on subsequent MRI examinations. ⁸²RbCl PET time activity curve analysis was performed which comprised lesion SUVmax, contralateral normal brain SUVmax, and tumor to background ratios (TBmax).

Results: ⁸²RbCl demonstrates uptake greater than normal brain parenchyma in all lesions studied. Time activity curves demonstrated progressive uptake of ⁸²RbCl in all lesions without evidence of washout. While recurrent disease demonstrated a greater mean SUVmax compared to radiation necrosis, no statistically significant difference between lesion SUVmax nor TBmax was found (P>0.05).

Conclusions: ⁸²RbCl PET produces high-contrast uptake of both recurrent disease and radiation necrosis compared to normal brain. However, no statistically significant difference was found between recurrent tumor and radiation necrosis.

Nuclear medicine plays an increasingly important role in several neoplasms management through a theragnostic approach by which targeted molecular imaging and radiotherapy are obtained with the use of radionuclide pairs with similar characteristics. In some cases, nuclear theragnostic use a pair of agents with identical chemical and biological characteristics while in others are employed theragnostic molecules which are not chemically or biologically identical but show similar biodistribution (so-called "twins in spirit" radiopharmaceuticals). This strategy was developed for the first time over 75 years ago, when iodine-131 was used for diagnostic imaging, confirmation of target expression and radionuclide therapy of thyroid cancer. Other theragnostic approaches were subsequently introduced with significant clinical results and some of them are currently considered standard treatment for different cancers. However, as any other therapy, also nuclear theragnostic treatment carries the potential risk of early deterministic and late stochastic off-target adverse effects, generally minimal and easily managed. This article reviews the reported side effects and risks of the main radiopharmaceuticals used for nuclear theragnostic in oncology for the treatment of thyroid cancer, neuroendocrine neoplasms, adrenergic tumors, metastatic prostate cancer, and liver tumors. Selecting appropriate patients using a multidisciplinary approach, meticulous pretreatment planning and knowledge of methods permit to decrease the incidence of these potential side effects.

Background: Qualitative assessment using the Deauville five-point Scale (DS) is the gold standard for interim and end-of treatment positron-emission tomography (PET) interpretation in lymphoma. In the present study we assessed the reliability and the prognostic value of different semi- quantitative parameters in comparison with DS for interim PET (iPET) interpretation in Hodgkin lymphoma (HL).

Methods: A cohort of 82 out of 260 patients with advanced stage HL enrolled in the International Validation Study (IVS), scored as 3 to 5 by the expert panel was included in the present report. Two nuclear medicine physicians blinded to patient history, clinical data and treatment outcome reviewed independently the iPET using the following parameters: DS, SUVmax, SUVpeak of the most active lesion, Qmax (ratio of SUVmax of the lesion to liver SUVmax) and Qres (ratio of SUVpeak of the lesion to liver SUVmean). The optimal sensitivity, specificity, positive and negative predictive value to predict treatment outcome was calculated for all the above parameters with the receiver operator characteristics analysis.

Results: The prognostic value of all parameters were similar, the best cut-off value being 4 for DS (area under the curve [AUC], 0.81 95% CI: 0.72-0.90), 3.81 for SUVmax (AUC 0.82 95% CI: 0.73-0.91), 3.20 for SUVpeak (AUC 0.86 95% CI: 0.77-0.94), 1.07 for Qmax (AUC 0.84 95% CI: 0.75-0.93) and 1.38 for Qres (AUC 0.84 95% CI: 0.75-0.93). The reproducibility of different parameters was similar as the inter-observer variability measured with Cohen's kappa were 0.93 (95% CI: 0.84-1.01) for the DS, 0.88 (0.77-0.98) for SUVmax, 0.82 (0.70-0.95) for SUVpeak, 0.85 (0.74-0.97) for Qres and 0.78 (0.65-0.92) for Qmax. Due to the high specificity of SUVpeak (0.87) and to the good sensitivity of DS (0.86), upon the use of both parameters the positive predictive value increased from 0.65 of the DS alone to 0.79. When both parameters were positive in iPET, 3-years Failure-Free Survival (FFS) was significantly lower compared to patients whose iPET was interpreted with qualitative parameters only (DS 4 or 5): 21% vs. 35%. On the other hand, the FFS of patients with negative results was not significantly different (88% vs. 86%).

Conclusions: In this study we demonstrated that, combining semi-quantitative parameters with SUVpeak to a pure qualitative interpretation key with DS, it is possible to increase the positive predictive value of iPET and to identify with higher precision the patients subset with a very dismal prognosis. However, these retrospective findings should be confirmed prospectively in a larger patient cohort.

Nuclear medicine therapeutic procedures have considerably expanded over the last few years, and their number is expected to grow exponentially in the future. Internal dosimetry has significantly developed as well, but has not yet been uniformly accepted as a valuable tool for prediction of therapeutic efficacy and toxicity. In this paper, we briefly summarize some of the arguments about the implementation of internal dosimetry in clinical practice. In addition, we provide a few examples of radionuclide anticancer therapies for which internal dosimetry demonstrated a significant impact on treatment optimization and patient outcome.

Theragnostics embraces "gnosis" and "prognosis" and concerns a treatment strategy which combines diagnostics with therapeutics. The birth of what we call today theragnostics can be traced in 1936, with the proposal of radioiodine, the first radiopharmaceutical approved in 1951 by FDA, in USA, as 131I sodium iodide. In 1957, 89Sr was also approved as first therapeutic radiotracer for skeletal metastases, followed in the subsequent years by 186Rh, 153Sm and, more recently, 223Ra, the first alpha emitter clinically utilized, allowing curative results and not only a palliative effect. Proposed in first eighties as [131I] Metaiodobenzylguanidine (MIBG), the theragnostic couple 123I/131I MIBG is still used in neural crest tumors, while, starting from partially unsatisfactory results in 70's, models based on antibodies for radioimmunoscintigraphy/radioimmunotherapy have been subsequently upgraded thanks to the introduction of monoclonal antibodies and other significant biological and technical improvements. The "Theragnostics called with this name" can be dated to early 90's with the first proposal of the somatostatin model, actually widely operating in neuroendocrine tumors with radio-chelates usable for diagnosis and therapy. Since then, many investigators are working on new theragnostics agents, also outside of the nuclear medicine, based on peptides, antibodies and other tools to find new models applicable in the clinical practice. The fast growth is stimulated by the interest of big pharma. Theragnostic concepts are the roots of nuclear medicine and new great goals are soon to be achieved in the direction of an increasing precision and tailored medicine.

Prostate-specific membrane antigen (PSMA) is a molecular target for both imaging diagnostics and therapeutics, i.e., a theragnostics target. There has been a growing body of evidence supporting PSMA theragnostics approaches in the management of prostate cancer (PCa) for tailored precision medicine. Tumor characterization through PSMA-ligand PET imaging is crucial for assessing the molecular signature and eligibility for PSMA radioligand therapy. Recent U.S. Food and Drug Administration (FDA) approval of two new drug applications for PSMA PET imaging contribute to reinforce PSMA as an oncologic blockbuster. Additionally, relevant progress in the PSMA treatment has been made in the last five years. [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy for patients with progressive PSMA-avid metastatic castration-resistant PCa (mCRPC) significantly increased overall survival and radiographic progression-free survival, according to the results of an international, prospective, open label, multicenter, randomized, phase III study (VISION trial). The objective of this comprehensive review is to highlight the recent advances in PCa theragnostics, focusing on actual clinical applications and future perspectives.

Background: Advanced age is an independent poor prognostic factor of diffuse large B-cell lymphoma (DLBCL). PMitCEBO (mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone) is an alternative to the cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen to decrease side effects in elderly patients. Many studies have shown prognostic value of an interim FDG PET-CT to predict survival. A recent consensus (ICML, Lugano 2013) has suggested using the 5-point scale Deauville criteria instead of those of the International Harmonization Project (IHP) to visually assess the response on interim PET. The objective of this study was to evaluate the prognostic value of an interim FDG PET-CT in patients older than 60 with treated DLBCL and to compare IHP and 5-PS Deauville visual interpretation to predict survival.

Methods: Forty-eight patients (mean age 73.2±5.2 years) treated by R-PMitCEBO for DLBCL undergoing FDG PET-CT before and after 3 cycles of treatment were retrospectively included. Event-free survival and overall survival were determined by Kaplan-Meier method and compared with interim PET-CT results using IHP and 5-PS Deauville criteria.

Results: Interim PET results using 5-PS Deauville criteria were significantly correlated with EFS (P<0.0001) and OS (P=0.001) whereas they were moderately correlated with EFS (P=0.046) and not with OS (P=0.106) using IHP criteria. Two-year EFS and OS rates were 86.5% and 89.2%, respectively, for patients in 1-3 score group, and 27.3% and 36.4%, respectively, for patients in ≥4 score group using the Deauville criteria.

Conclusions: Our results confirmed the prognostic value of an interim PET-CT in elderly patients with DLBCL and the better performance of the 5-PS Deauville criteria.