Free TcO 4- in 99m Tc-PSMA Scan : A Case Report and Review of an Old Pitfall in the New Era of Modern Imaging.

ABSTRACT: In a recent 99m Tc-HYNIC-PSMA study conducted at our department, we examined 2 patients with prostate cancer referred for initial staging on the same day. The whole-body scans revealed radiotracer uptake in the gastric mucosa and thyroid glands, alluding to high levels of free TcO 4- in the injected vial. The scans were repeated after confirming acceptable radiopharmaceutical purity of 97% (normal range, 95%-100%). Interestingly, 1 patient had liver metastases at presentation, which remained non-PSMA-avid after repeating the scan. We have reviewed this pitfall, which has been reported with many radiotracers, yet not reported with PSMA tracers.

99m Tc-HYNIC-FAPI-46 SPECT/CT Uptake in Lactating Breasts.

ABSTRACT: A 36-year-old woman with a history of medullary thyroid carcinoma was referred for 99m Tc-HYNIC-FAPI-46 scan. Her calcitonin levels gradually increased after external beam radiation therapy, whereas her CEA levels were stable. A few suspicious tumoral lymphadenopathies were localized to the superior mediastinum. Interestingly, bilateral physiologic breast uptake was noticed, which was presumed to be due to lactation in the past 18 months. To our knowledge, physiologic breast uptake in 99m Tc-HYNIC-FAPI imaging has not been previously reported.

Quadruplet Therapy in De Novo High-Volume Mixed Neuroendocrine Prostate Cancer Using 177Lu-PSMA: A Case Report.

ABSTRACT: We present a case of de novo high-volume metastatic prostate cancer with high PSMA expression, partially PSMA-negative, using quadruplet therapy (PROMISE ver. 2 miTNM; miT4N2M1aM1b(dmi) PRIMARY score: 5, PSMA-expression score: 0-3). Because of our patient's partial PSMA negativity and after a multidisciplinary tumor board discussion, we decided to use a modified protocol involving doublet hormonal therapy along with 177Lu-PSMA and radiation therapy to address the PSMA-negative disease. The patient responded well to this treatment, but recurrence was ultimately inevitable. This case represents a typical example of mixed neuroendocrine prostate carcinoma and highlights its resistant phenotype in response to quadruplet therapy.

A dataset of [68Ga]Ga-Pentixafor PET/CT images of patients with high-grade Glioma.

This paper contains single-center prospective information showing illustrative examples of chemokine receptor-4 (CXCR4) targeting in high-grade glial brain tumors in treatment-naïve adult patients using a novel radiolabeled PET tracer: [68Ga]Ga-CXCR4 PET/CT. High-grade glioma is one of the most resistant malignancies to treatment. Despite major breakthroughs in diagnostic and therapeutic approaches, the overall 5-year survival rate remains in the 5-10% range. CXCR4 is a chemokine with the C-X-C motif that is overexpressed in high-grade gliomas. The 24 consecutive treatment- naïve enrolled patients underwent PET/CT images using the SIEMENS scanner (Biograph6 TrueV) and received the radiotracer intravenously. After approximately 60 min, the PET/CT acquisition was performed with a dedicated scanner and in 10 min time per bed position. The images were reconstructed and analyzed with the 3D-OSEM algorithm, applying point spread function (PSF) or resolution recovery algorithm (TrueX in Syngo ® software, Siemens Medical Solution), 3 iterations, and 21 subsets using a 3 mm Gaussian post-smoothing filter. These data would be potentially beneficial for automatic tumor delineation machine learning after augmented with other data retrieved from different papers as well as for differentiation between an active viable tumor vs. post-surgery/necrosis in indeterminate cases. The theranostics potential (CXCR4-tageted labeled beta emitters) is one of the most novel areas of interest for future studies.

[68Ga] Ga-Pentixafor diffuse bilateral Adrenal & Breast uptake in a patient with High-grade Glioma: A note of caution on normal variants.

[68Ga] Ga-labeled C-X-C motif receptor4 as a novel radio-ligand using PET/CT has been investigated for tracing various kinds of solid and hematopoietic malignancies in recent years. High-grade Glioma (WHO classification 2016 grade III and IV) shows elevated levels of CXCR4 ligand expression in the affected tumoral cells. Healthy and non-affected organ cells express low-level CXCR4 ligands density. We performed [68Ga] Ga-Pentixafor (Pars-Cixafor™) PET/CT in a patient with high-grade Glioma (anaplastic oligodendroglioma WHO grade III) with no other documented medical condition and history. In addition to the Pentixafor-avid tumor remnant in the PET/CT images, we observed mild symmetrical bilateral uptake in the fibro glandular tissue of the breasts and moderate CXCR4(Pentixafor) avidity in both adrenal glands without any discernable pathology and abnormal density changes in the CT component of the study. Attention should be paid to the interpreting [68Ga] Ga-Pentixafor PET/CT examination and its normal uptakes and variants.

Interesting Findings in 68 Ga-FAPI-46 PET/CT Imaging in a Patient With Glioblastoma Multiforme.

ABSTRACT: A 55-year-old disabled man with glioblastoma multiforme was referred to us for fibroblast activation protein inhibitor (FAPI) PET/CT imaging. 68 Ga-DOTA-FAPI-46 scan revealed uptake in the primary tumor and unexpected uptakes in soft tissue, especially in periarticular regions. These latter foci were compatible with calcifications on the CT. One in the breast was compatible with fibrotic tissue, but 2 other foci, in the rectus abdominis and gallbladder wall, could not be correlated with the CT findings. In Neurogenic heterotopic ossification, hypoxia-associated oxidative stress results in the metaplastic transformation of fibroblasts. Abnormal differentiation of fibroblasts in neurogenic heterotopic ossification before ossification could explain radiolabeled FAPI avidity in the mentioned areas.

68 Ga-FAPI-46 PET/CT in a Metastatic Castration-Resistant Prostate Cancer Patient With Low PSMA Expression.

ABSTRACT: A 70-year-old man with mCRPC (metastatic castration-resistant prostate cancer) was referred for 68 Ga-PSMA PET/CT for restaging and the possibility of targeted molecular radioligand therapy with 177 Lu-PSMA. Numerous 68 Ga-PSMA-avid skeletal metastases with low SUVs were noted. Because of low PSMA expression, a 68 Ga-FAPI-46 PET/CT was performed to evaluate the eligibility for FAPI-based radioligand therapy. There were some discordant findings between 68 Ga-PSMA and 68 Ga-FAPI PET/CT scans regarding the detectability of lesions and SUVs. Our case signifies that 68 Ga-FAPI theragnostic may have a potential role in the treatment of mCRPC patients with insignificant PSMA expression or in cases after the failure of 177 Lu-PSMA therapy.

Bone scan with technetium 99m-methyl diphosphonate, the missing link in the initial staging of muscle-invasive bladder carcinoma.

BACKGROUND: Accurate staging is crucial to determine the type of treatment for patients with bladder cancer (BCa), especially in high-risk cases. We aimed to assess the role of bone scan in the initial staging of muscle-invasive bladder carcinoma (MIBC). MATERIAL AND METHODS: Forty-five patients with MIBC were referred to our tertiary clinic to perform a technetium 99m-methyl diphosphonate (Tc99m-MDP) bone scan from January 2019 to March 2020. The patients underwent bone scintigraphy with pelvic SPECT/CT before radical cystectomy. Whole-body scanning was performed 4 hours after Tc99m-MDP injection in both anterior and posterior views. Since the most common bone involvement site in these patients is the pelvic bones and the spine, pelvic SPECT/CT was performed in all patients. RESULTS: Frequency of skeletal metastasis was 26.7%. Only 19% of the metastases were detected by previous pelvic CT/MRI images performed for routine staging. All the reported skeletal metastases by previous anatomical imaging methods were detected in the bone scan. There was no statistically significant correlation between bone metastasis and the patient's age, lymph nodes metastasis (LNM), hydronephrosis, and muscle-invasive type. The mean serum calcium level was 8.7 ± 0.57 in patients with bone metastasis and 8.87 ± 0.99 in patients without bone metastasis, which was not statistically significant. CONCLUSION: Bone scan has higher diagnostic performance than conventional imaging methods for detecting bone metastases. It changed the management plan in 8.8% of our patients, so we conclude that performing a whole-body bone scan in the initial staging of MIBC would be helpful.

Peptide receptor radionuclide therapy (PRRT) in radioiodine-refractory thyroid cancer: A case report of significant response to lu177 DOTA-TATE treatment

SUMMARY A 59-year-old woman with follicular thyroid carcinoma underwent total thyroidectomy followed by radioiodine treatment. Following treatment, the whole-body scan did not show any abnormal radioiodine uptake. However, during the follow-up, the serum thyroglobulin (Tg) value increased without detectable thyroglobulin-antibodies. We performed a Ga-68 DOTA-TATE PET/CT showing a sternal lesion and several lung nodules with high somatostatin receptor density. Also, on the next day, FDG PET/CT was performed, which confirmed the findings. Considering the high levels of somatostatin receptor expression in such metastases, we planned lu177 DOTA-TATE therapy. After two cycles of lu177 DOTA-TATE injection, serum thyroglobulin significantly dropped, and she claimed that her sternal pain and dyspnea were much better. This was the case of a patient suffering from iodine-refractory follicular thyroid carcinoma, with somatostatin-receptor expression, treated with 177Lu-DOTA-TATE, showing a significant response.

Could Fibroblast Activation Protein (FAP)-Specific Radioligands Be Considered as Pan-Tumor Agents?

Background: Cancer-associated fibroblasts (CAFs) can strongly modulate the response to therapy of malignant tumor cells, facilitating their continuous proliferation and invading behaviors. In this context, several efforts were made in identifying the fibroblast activation protein (FAP) as a CAF recognizer and in designing FAP-specific PET radiotracers (as 68Ga-FAPI) along with FAP-specific therapeutic radioligands. Herein, we review different clinical studies using the various FAP-specific radioligands as novel theranostic agents in a wide range of oncologic and nononcologic indications. Methods: A comprehensive systematic search was conducted on the PubMed and Scopus databases to find relevant published articles concerning the FAP-specific PET imaging as well as the FAP-specific radionuclide therapy in patients with oncologic and nononcologic indications. The enrolled studies were dichotomized into oncologic and nononcologic categories, and the required data were extracted by precisely reviewing the whole text of each eligible study. A meta-analysis was also performed comparing the detection rates of 68Ga-FAPI vs. 18F-FDG PET/CT using odds ratio (OR) and risk difference as outcome measures. Results: Of the initial 364 relevant papers, 49 eligible articles (1479 patients) and 55 case reports were enrolled in our systematic review. These studies observed high radiolabeled FAPI avidity as early as 10 minutes after administration in primary sites of various malignant tumors. Based on the meta-analysis which was done on the reported detection rates of the 68Ga-FAPI and 18F-FDG PET/CT scans, the highest OR belonged to the primary lesion detection rate of gastrointestinal tumors (OR = 32.079, 95% CI: 4.001-257.212; p = 0.001) with low heterogeneity (I2 = 0%). The corresponding value of the nodal metastases belonged to hepatobiliary tumors (OR = 11.609, 95% CI: 1.888-71.365; p = 0.008) with low heterogeneity (I2 = 0%). For distant metastases, the highest estimated OR belonged to nasopharyngeal carcinomas (OR = 77.451, 95% CI: 7.323-819.201; p < 0.001) with low heterogeneity (I2 = 0%). Conclusions: The outperformance of 68Ga-FAPI PET/CT over 18F-FDG PET/CT in identifying certain primary tumors as well as in detecting their metastatic lesions may open indications for evaluation of cases with inconclusive 18F-FDG PET/CT findings. What needs to be emphasized is that the false-positive results might be problematic and must be taken into account in 68Ga-FAPI PET/CT interpretation. More clarification on the role of FAPI radioligands in oncologic imaging, radionuclide therapy, and radiotherapy treatment planning is therefore required.

Peptide receptor radionuclide therapy (PRRT) in radioiodine-refractory thyroid cancer: A case report of significant response to lu177 DOTA-TATE treatment.

A 59-year-old woman with follicular thyroid carcinoma underwent total thyroidectomy followed by radioiodine treatment. Following treatment, the whole-body scan did not show any abnormal radioiodine uptake. However, during the follow-up, the serum thyroglobulin (Tg) value increased without detectable thyroglobulin-antibodies. We performed a Ga-68 DOTA-TATE PET/CT showing a sternal lesion and several lung nodules with high somatostatin receptor density. Also, on the next day, FDG PET/CT was performed, which confirmed the findings. Considering the high levels of somatostatin receptor expression in such metastases, we planned lu177 DOTA-TATE therapy. After two cycles of lu177 DOTA-TATE injection, serum thyroglobulin significantly dropped, and she claimed that her sternal pain and dyspnea were much better. This was the case of a patient suffering from iodine-refractory follicular thyroid carcinoma, with somatostatin-receptor expression, treated with 177Lu-DOTA-TATE, showing a significant response.

Fibroblast Activation Protein Inhibitor Imaging and Therapy in a Patient With Multiple Endocrine Neoplasia Type 2A Syndrome.

ABSTRACT: A patient with multiple endocrine neoplasia type 2A syndrome who had exhausted several surgeries and radiotherapy was referred to nuclear medicine department for theranostic approaches. [68Ga]-DOTATATE PET/CT and [131I]I-mIBG SPECT/CT were performed, but the degree of uptake was insufficient for using the treatment companion of these tracers. Finally, 1 year later, [68Ga]-FAPI-46 PET/CT showed progressive disease with metastases to the lung, liver, bone, and lymph nodes with intense [68Ga]-FAPI-46 uptake. Treatment with [177Lu]Lu-FAPI-46 was done, and the patient tolerated treatment and showed evidence of clinical improvement following therapy.

Efficacy, safety and prognostic factors affecting overall survival among metastatic prostate cancer patients undergoing treatment with 177Lu-PSMA-617: A single center study.

BACKGROUND: Determining the efficacy, safety, and prognostic factors affecting overall survival (OS) among metastatic prostate cancer patients undergoing PSMA-targeted radioligand therapy (PRLT). METHOD: In this retrospective study, from November 2016 and December 2019, 43 heavily pretreated (90.7% on 1st line androgen deprivation therapy (ADT), 53.5% on 2nd line ADT, 58.1% on docetaxel) metastatic prostate cancer patients with median age of 71 years (range: 51-88 years) were enrolled. Treatment cycles were repeated every 8 weeks (range: 6-12 weeks). To evaluate the biochemical response after each cycle, prostate specific antigen (PSA) levels were measured and analyzed according to the Prostate Cancer Working Group 3 (PCWG3) criteria cutoffs. Possible adverse events after therapy were retrospectively classified according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. Kaplan-Meier and multivariable Cox proportional hazard regression analyses were used to identify factors associated with OS. RESULTS: A total of 112 cycles of PRLT with a median of 3 cycles (range: 1-6) and median administered activity per cycle of 6.29 GBq (range: 4.45-7.7 GBq) were used. PSA decline was observed in 65.1% of patients, and best PSA decline of ≥50% and ≥90% were achieved in 39.5% and 23.3% of patients, respectively. Major (grade III) anemia and thrombocytopenia occurred in 11.6% and 7% of patients, respectively. Median OS and median PSA progression-free survival were 52 and 20 weeks, respectively. In univariate analysis, baseline hemoglobin <11.2 g/dL, baseline platelets count ≥327,000/µL, PSA decline <20.94% after first cycle of therapy, Eastern Cooperative Oncology Group (ECOG) >2, baseline PSA ≥ 115 ng/mL, cumulative dose of 177Lu-PSMA <12.95 GBq, initial alkaline phosphatase ≥196.5 U/L, initial lactate dehydrogenase ≥380 U/L and superscan pattern in bone scintigraphy were associated with worse OS. In multivariable Cox regression analysis, higher baseline platelet count, lower baseline hemoglobin, superscan pattern, and lower cumulative dose of 177Lu-PSMA remained significant predictors of poor OS. CONCLUSION: PRLT with 177Lu-PSMA is well-tolerated and effective in metastatic prostate cancer patients who have no other treatment options available. The novel prognostic markers found in this study (high platelet count, superscan pattern) were associated with poor overall survival.

Head-to-Head Comparison of Fibroblast Activation Protein Inhibitors (FAPI) Radiotracers versus [18F]F-FDG in Oncology: A Systematic Review.

Several recent studies comparing radiolabeled fibroblast activation protein inhibitors (FAPI) and fluorine-18 fluorodeoxyglucose ([18F]F-FDG) as positron emission tomography (PET) radiotracers in oncology have been published. The aim of this systematic review is to perform an updated evidence-based summary about the comparison of these PET radiotracers in oncology to better address further research in this setting. Studies or subsets of studies comparing radiolabeled FAPI and [18F]F-FDG as PET radiotracers in oncology were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until August 2021. Literature data about the comparison of [18F]F-FDG and radiolabeled FAPI are rapidly increasing. Overall, taking into account radiotracer uptake and tumor-to-background uptake ratio, compared to [18F]F-FDG PET, an equal or higher detection of primary tumors and/or metastatic lesions was usually demonstrated by using radiolabeled FAPI PET. In particular, the cancer entities with better detection rate of tumor lesions by using radiolabeled FAPI PET, compared to [18F]F-FDG PET, were gastrointestinal tumors, liver tumors, breast cancer and nasopharyngeal carcinoma. Further comparison studies are needed to better evaluate the best field of application of radiolabeled FAPI PET.

Incidental finding of a dermoid cyst in a whole-body iodine scan: importance of using [131I]SPECT/CT in the differentiated thyroid carcinoma.

A 33-year-old female with a history of total thyroidectomy for papillary thyroid carcinoma was referred to the nuclear medicine department for ablative radioiodine therapy. Post ablation scan showed an area of intense iodine uptake on the left side of the pelvic region, corresponding to the large well-defined heterogeneous mass in the left ovary in the SPECT/CT images. The radiologic features of this lesion were compatible with a dermoid cyst, previously unrecognized. Eventually, the lesion was laparoscopically removed, and a typical dermoid cyst was confirmed through histopathologic assessment.

Prostate Cancer With Neuroendocrine Differentiation Recurring After Treatment With 177Lu-PSMA: A Chance for 177Lu-DOTATATE Therapy?

ABSTRACT: Prostate cancer with NED (neuroendocrine differentiation) may occur in various stages of the disease, which is associated with a poor prognosis and treatment resistance. We present a case of a patient with metastatic castration-resistant prostatic cancer, who was treated with 7 cycles of 177Lu-PSMA and a very good response. Although only few foci with PSMA uptake were remained in the last posttreatment images, PSA levels dramatically began to rise. This raised suspicion for NED, and 68Ga-DOTATATE was done showing sufficient uptake to consider a trial of 177Lu-DOTATATE. The patient reported pain response, and PSA levels dropped after 1 cycle of the treatment.

99m Tc-Octreotide-Avid Brain Mass In A Patient With Poorly Differentiated Papillary Thyroid Carcinoma, Hope In Despair.

Brain metastases of PTC are rare and occur in 0.1-5% of the patients, especially in the poorly differentiated types that usually fail to concentrate iodine. We present a rare case of PTC with probable brain metastasis in a 58-year-old woman with a history of poorly differentiated PTC that showed elevated Tg levels and no metastasis was detected in the whole-body iodine scan, despite the positive 99m Tc-octreotide scintigraphy. This imaging modality could be helpful as a diagnostic guide for radionuclide therapy with labeled somatostatin analogs in cases of thyroid carcinoma with elevated Tg levels and negative whole-body iodine scan.

Whole-Body 177Lu-Prostate-Specific Membrane Antigen Scan Pattern With Excess Free 177Lu-Chloride in a Metastatic Castration-Resistant Prostate Cancer Patient.

A 56-year-old man with metastatic castration-resistant prostate cancer was referred for radioligand therapy with Lu-prostate-specific membrane antigen. In the third cycle, a posttherapy whole-body scan showed unexpected skeletal and joint uptake apart from his known metastatic lesions. This observation raised suspicion for possible impurity (mainly free lutetium) in the applied radiopharmaceutical product. After contacting the radiopharmaceutical company, we were informed that the radiochemical purity of the used batch of Lu-prostate-specific membrane antigen had been 95%. This is the first report of excess free lutetium scan pattern and its complications in a patient undergoing radioligand therapy.