Nuclear Medicine and Molecular Imaging

The Correlation Between Tenosynovitis Pattern on Two-Phase Bone Scintigraphy and Clinical Manifestation in Patients with Suspected Rheumatoid Arthritis Abstract Purpose To investigate the correlation between the tenosynovitis pattern on two-phase bone scintigraphy (2P-BS) and clinical manifestation in patients with suspected rheumatoid arthritis (RA). Method 2P-BS including technetium–99m-methylene diphosphonate blood pool and bone phase imaging in 402 consecutive patients with clinically suspected RA were retrospectively reviewed. According to 2010 RA Classification Criteria, patients were grouped as RA and non-RA. Visual assessment of all fingers, toes, wrists, and ankles on 2P-BS was performed. Clinical suspected tenosynovitis was evaluated on physical examination. Rheumatoid factor, anti-cyclic citrullinated protein antibody, C-reactive protein, and estimated sedimentation rate were obtained. Radiographic findings were also used to define early and established arthritis. Results Tenosynovitis pattern was detected in 12.7% (51/402 patients) on 2P-BS. A total of 94.1% (48/51) were diagnosed as RA vs. 5.9% (3/51) as non-RA. Of the 48 RA patients with positive 2P-BS finding, 85.4% (41/48) had early arthritis and 14.6% (7/48) had established arthritis. On physical examination, tenosynovitis was suspected in 21.9% (88/402). A total of 56.8% (50/88) belonged to the RA group and 43.2% (38/88) to the non-RA group. The tenosynovitis pattern of 2P-BS and physical examination showed statistical difference and moderate agreement. The positive tenosynovitis pattern on 2P-BS represented up to 26.408 of odds ratio which was highest among the RA-associated factors. Conclusion Tenosynovitis pattern on 2P-BS was more commonly detected in the RA group and was more frequently associated with early arthritis pattern. Therefore, 2P-BS could give additional information for the detection of subclinical tenosynovitis in early or preclinical RA patients.

Ipsilateral Hyperhidrosis: Atypical Symptom of Small Lung Adenocarcinoma Evaluated by 18 F-FDG PET-CT Abstract A 45-year-old male visited our clinic due to right palmar anhidrosis and contralateral hyperhidrosis. Chest computed tomography (CT) showed a solitary pulmonary nodule with mediastinal lymph node enlargement, but a cause for atypical palmar anhidrosis was not identified. Subsequent fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed (PET/CT) revealed a localized pleural metastasis at the right apex with direct invasion of the paravertebral sympathetic chain. The pleural metastasis, which was not seen on chest CT, evoked ipsilateral anhidrosis independent of a mass effect or direct invasion by the primary lung tumor. 18F-FDG PET/CT can be helpful in identifying the cause of atypical symptoms in patient with small sized lung cancer.

Perspectives in Radiomics for Personalized Medicine and Theranostics Abstract Radiomics handles imaging biomarker from high-throughput feature extraction through complex pattern recognition that is difficult for human to process. Recent medical paradigms are rapidly changing to personalized medicine, including molecular targeted therapy, immunotherapy, and theranostics, and the importance of biomarkers for these is growing day by day. Even though biopsy continues to gold standard for tumor assessment in personalized medicine, imaging is expected to complement biopsy because it allows whole tumor evaluation, whole body evaluation, and non-invasive and repetitive evaluation. Radiomics is known as a useful method to get imaging biomarkers related to intratumor heterogeneity in molecular targeted therapy as well as one-size-fits-all therapy. It is also expected to be useful in new paradigms such as immunotherapy and somatostatin receptor (SSTR) or prostate-specific membrane antigen (PSMA)-targeted theranostics. Radiomics research should move to multimodality (CT, MR, PET, etc.), multicenter, and prospective studies from current single modality, single institution, and retrospective studies. Image-quality harmonization, intertumor heterogeneity, and integrative analysis of information from different scales are thought to be important keywords in future radiomics research. It is clear that radiomics will play an important role in personalized medicine.

Lesion-Wise Comparison of Pre-Therapy and Post-Therapy Effective Half-Life of Iodine-131 in Pediatric and Young Adult Patients with Differentiated Thyroid Cancer Undergoing Radioiodine Therapy Abstract Purpose The effective half-life of radioiodine is an important parameter for dosimetry in differentiated thyroid cancer patients, particularly in children. We determined the pre-therapy and post-therapy effective half-life in different types of lesions, i.e., remnant, node, or lung metastases. Methods Of 84 patients recruited, 27 were < 18 years (group 1) and the remaining 57 were between 18 and 21 years (group 2). A total of 114 studies were conducted and 253 lesions were analyzed. Serial whole-body scans were acquired at 24, 48, and ≥ 72 h after administration of iodine-131. Region of interests was drawn over lesions to determine counts in the lesion. Time versus counts graphs were plotted and mono-exponentially fitted to determine effective half-life. Results The post-therapy effective half-life was found to be lesser than pre-therapy effective half-life in all types of lesions and in all groups. Median effective half-life was found maximum in intact lobe, minimum in the lung, and intermediate in remnant and nodes. In the assessment of all lesions together, pre- and post-therapy median and interquartile range (IQR) effective half-life were 59.8 (37–112) h and 48.6 (35.2–70.8) h (p < 0.0001) in group 1, 73.9 (46.2–112.7) h and 60 (57.4–85.9) h (p < 0.0001) in group 2, and 68.6 (41.53–112.36) h and 54.7 (36–80.6) h (p < 0.0001) in combined group, respectively. Importantly, the pre- and post-therapy median effective half-life serially dropped after each successive cycles of iodine-131. Conclusions There was a significant difference in pre-therapy and post-therapy effective half-life in all types of lesions. These results may have implications in calculating the correct therapeutic dose in children and in young adults.

Clinical Applications of Technetium-99m Quantitative Single-Photon Emission Computed Tomography/Computed Tomography Abstract Single-photon emission computed tomography/computed tomography (SPECT/CT) is an already established nuclear imaging modality. Co-registration of functional information (SPECT) with anatomical images (CT) paved the way to the wider application of SPECT. Recent advancements in quantitative SPECT/CT have made it possible to incorporate quantitative parameters, such as standardized uptake value (SUV) or %injected dose (%ID), in gamma camera imaging. This is indeed a paradigm shift in gamma camera imaging from qualitative to quantitative evaluation. In fact, such quantitative approaches of nuclear imaging have only been accomplished for positron emission tomography (PET) technology. Attenuation correction, scatter correction, and resolution recovery are the three main features that enabled quantitative SPECT/CT. Further technical improvements are being achieved for partial-volume correction, motion correction, and dead-time correction. The reported clinical applications for quantitative SPECT/CT are mainly related to Tc-99m-labeled radiopharmaceuticals: Tc-99m diphosphonate for bone/joint diseases, Tc-99m pertechnetate for thyroid function, and Tc-99m diethylenetriaminepentaacetic acid for measurement of glomerular filtration rate. Dosimetry before trans-arterial radio-embolization is also a promising application for Tc-99m macro-aggregated albumin. In this review, clinical applications of Tc-99m quantitative SPECT/CT will be discussed.

Eruption of Metastatic Paraganglioma After Successful Therapy with 177 Lu/ 90 Y-DOTATOC and 177 Lu-DOTATATE Abstract Metastatic paraganglioma treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been introduced as a novel management option for metastatic neuroendocrine tumors demonstrating safety, efficacy, and increased quality of life. We present two cases of marked progression of metastatic paraganglioma following initial partial response to PRRT. Given their positivity on 68Ga-DOTATATE PET/CT and 111In-octreotide SPECT, they underwent PRRT. Imaging following treatment revealed significant improvement in size and intensity, with some foci nearly completely resolved in one patient, and disease regression with a decrease in the number and size of bone and liver lesions in the second patient. Within months, repeat imaging in both patients revealed extensive metastatic disease with new lesions, which eventually lead to their deaths. The mechanism for rapid disease progression after partial response is not well understood, although it could be related to initially high Ki-67 levels or 18F-FDG PET/CT SUVmax values. However, naturally rapid disease progression despite PRRT response cannot be excluded. This finding warrants the importance of proper patient counseling along with early and accurate pre-PRRT assessment, taking into consideration the above potential risk factors for therapy response in order to personalize treatment regimens and achieve maximum patient benefit. ClinicalTrials.gov Identifier NCT00004847

Perspectives for Concepts of Individualized Radionuclide Therapy, Molecular Radiotherapy, and Theranostic Approaches Abstract Radionuclide therapy (RNT) stands on the delivery of radiation to tumors or non-tumor target organs using radiopharmaceuticals that are designed to have specific affinity to targets. RNT is recently called molecular radiotherapy (MRT) by some advocators in order to emphasize its characteristics as radiotherapy and the relevance of dosimetry-guided optimization of treatment. Moreover, RNT requires relevant radiation protection standards because it employs unsealed radionuclides and gives therapeutic radiation doses in humans. On the basis of these radiation protection standards, the development and use of radiopharmaceuticals for combined application through diagnostics and therapeutics lead to theranostic approaches that will enhance the efficacy and safety of treatment by implementing dosimetry-based individualization.

Use of Molecular Imaging in Clinical Drug Development: a Systematic Review Abstract Background Molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can provide the crucial pharmacokinetic-pharmacodynamic information of a drug non-invasively at an early stage of clinical drug development. Nevertheless, not much has been known how molecular imaging has been actually used in drug development studies. Methods We searched PubMed using such keywords as molecular imaging, PET, SPECT, drug development, and new drug, or any combination of those to select papers in English, published from January 1, 1990, to December 31, 2015. The information about the publication year, therapeutic area of a drug candidate, drug development phase, and imaging modality and utility of imaging were extracted. Results Of 10,264 papers initially screened, 208 papers met the eligibility criteria. The more recent the publication year, the bigger the number of papers, particularly since 2010. The two major therapeutic areas using molecular imaging to develop drugs were oncology (47.6%) and the central nervous system (CNS, 36.5%), in which efficacy (63.5%) and proof-of-concept through either receptor occupancy (RO) or other than RO (29.7%), respectively, were the primary utility of molecular imaging. PET was used 4.7 times more frequently than SPECT. Molecular imaging was most frequently used in phase I clinical trials (40.8%), whereas it was employed rarely in phase 0 or exploratory IND studies (1.4%). Conclusions The present study confirmed the trend that molecular imaging has been more actively employed in recent clinical drug development studies although its adoption was rather slow and rare in phase 0 studies.

Clinical Personal Connectomics Using Hybrid PET/MRI Abstract Brain connectivity can now be studied with topological analysis using persistent homology. It overcame the arbitrariness of thresholding to make binary graphs for comparison between disease and normal control groups. Resting-state fMRI can yield personal interregional brain connectivity based on perfusion signal on MRI on individual subject bases and FDG PET produces the topography of glucose metabolism. Assuming metabolism perfusion coupling and disregarding the slight difference of representing time of metabolism (before image acquisition) and representing time of perfusion (during image acquisition), topography of brain metabolism on FDG PET and topologically analyzed brain connectivity on resting-state fMRI might be related to yield personal connectomics of individual subjects and even individual patients. The work of association of FDG PET/resting-state fMRI is yet to be warranted; however, the statistics behind the group comparison of connectivity on FDG PET or resting-state MRI was already developed. Before going further into the connectomics construction using directed weighted brain graphs of FDG PET or resting-state fMRI, I detailed in this review the plausibility of using hybrid PET/MRI to enable the interpretation of personal connectomics which can lead to the clinical use of brain connectivity in the near future.

Quantitative Imaging of Alpha-Emitting Therapeutic Radiopharmaceuticals Abstract Targeted alpha therapy (TAT) is an active area of drug development as a highly specific and highly potent therapeutic modality that can be applied to many types of late-stage cancers. In order to properly evaluate its safety and efficacy, understanding biokinetics of alpha-emitting radiopharmaceuticals is essential. Quantitative imaging of alpha-emitting radiopharmaceuticals is often possible via imaging of gammas and positrons produced during complex decay chains of these radionuclides. Analysis of the complex decay chains for alpha-emitting radionuclides (Tb-149, At-211, Bi-212 (decayed from Pb-212), Bi-213, Ra-223, Ac-225, and Th-227) with relevance to imageable signals is attempted in this mini-review article. Gamma camera imaging, single-photon emission computed tomography, positron emission tomography, bremsstrahlung radiation imaging, Cerenkov luminescence imaging, and Compton cameras are briefly discussed as modalities for imaging alpha-emitting radiopharmaceuticals.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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6948891480

alsfakia@gmail.com