Thabo Lengana

68Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients

BackgroundTo report on imaging findings using 68Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients.Methods68Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status.ResultsOut of 81 tumor lesions identified, 84% were identified on 68Ga-PSMA-HBED-CC PET. 68Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p = 0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p = 0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and 68Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r = 0.407, p = 0.015).Conclusions68Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry.

68Ga-PSMA PET/CT impact on prostate cancer management

The objective of this study was to assess the impact of 68Ga-prostate-specific membrane antigen (68Ga-PSMA) PET/CT on the management of prostate cancer in patients with biochemical recurrence (BCR). Methods: Documented management plans before and after 68Ga-PSMA PET/CT in 100 patients with BCR were retrospectively reviewed, and changes in plans were recorded. Results: Management changed after 68Ga-PSMA PET/CT in 39 patients (39%). The management changes occurred in 23 (33.8%) of 68 patients with radical prostatectomy and 16 (50%) of 32 patients previously treated with radical radiotherapy. Positive scan results (P < 0.001) and higher prostate-specific antigen (PSA) levels (P = 0.024) were associated with management changes. No significant association with management change was found for Gleason grade, stage, presence of metastatic disease, PSA velocity, or PSA doubling time. Conclusion: 68Ga-PSMA PET/CT altered management in 39% of patients with BCR, and changes occurred more often in patients with radical radiotherapy treatment, positive 68Ga-PSMA scan results, and higher PSA levels.

Intra-individual comparison of 18F-PSMA-1007 and 18F-DCFPyL PET/CT in the prospective evaluation of patients with newly diagnosed prostate carcinoma: A pilot study

The introduction of 18F-labeled prostate-specific membrane antigen (PSMA)–targeted PET/CT tracers, first 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) and more recently 18F-PSMA-1007 (((3S,10S,14S)-1-(4-(((S)-4-carboxy-2-((S)-4-carboxy-2-(6-18F-fluoronicotinamido)butanamido)butanamido)methyl)phenyl)-3-(naphthalen-2-ylmethyl)-1,4,12-trioxo-2,5,11,13-tetraazahexadecane-10,14,16-tricarboxylic acid)), have demonstrated promising results for the diagnostic workup of prostate cancer. This clinical study presents an intraindividual comparison to evaluate tracer-specific characteristics of 18F-DCFPyL versus 18F-PSMA-1007. Methods: Twelve prostate cancer patients, drug-naïve or before surgery, received similar activities of about 250 MBq of 18F-DCFPyL and 18F-PSMA-1007 48 h apart and were imaged 2 h after injection on the same PET/CT scanner using the same reconstruction algorithm. Normal-organ biodistribution and tumor uptake were quantified using SUVmax. Results: PSMA-positive lesions were detected in 12 of 12 prostate cancer patients. Both tracers, 18F-DCFPyL and 18F-PSMA-1007, detected the same lesions. No statistical significance could be observed when comparing the SUVmax of 18F-DCFPyL and 18F-PSMA-1007 for local tumor, lymph node metastases, and bone metastases. With regard to normal organs, 18F-DCFPyL had statistically significant higher uptake in kidneys, urinary bladder, and lacrimal gland. Vice versa, significantly higher uptake of 18F-PSMA-1007 in muscle, submandibular and sublingual gland, spleen, pancreas, liver, and gallbladder was observed. Conclusion: Excellent imaging quality was achieved with both 18F-DCFPyL and 18F-PSMA-1007, resulting in identical clinical findings for the evaluated routine situations. Nonurinary excretion of 18F-PSMA-1007 might present some advantage with regard to delineation of local recurrence or pelvic lymph node metastasis in selected patients; the lower hepatic background might favor 18F-DCFPyL in late stages, when rare cases of liver metastases can occur.

18F-FDG PET/CT in the detection of asymptomatic malignant melanoma recurrence

AIM To evaluate the diagnostic accuracy of FDG PET/CT in the detection of asymptomatic recurrence in patients with malignant melanoma who have had resection of their primary lesion. We also aimed to determine the pattern and factors predisposing to disease recurrence. METHODS Patients with malignant melanoma who have had surgical resection of their disease and without any clinical evidence of disease recurrence were followed-up with FDG PET/CT. The diagnostic accuracy of FDG PET/CT, pattern of recurrence and factors predictive of disease recurrence were determined. RESULTS A total of 144 patients were followed-up for a median period of 50.50 months. Asymptomatic recurrence was seen in 37 patients (25.7 %) with a median time to recurrence of 20 months. Lymph node was the commonest site of asymptomatic recurrence. Sex, tumour depth, histology type and presence of nodal metastasis were significant predictors of tumour recurrence. Age, race, site of primary lesion, type of lymph node resection were not significant predictors of disease recurrence. Race has a significant effect on the histological subtype of tumour (nodular maligna was more common in Caucasian while acral lentiginous was more prevalent in the Blacks) and the site of the primary lesion (lower limb in Blacks and trunk in Caucasians). Sensitivity, specificity and accuracy of FDG PET/CT for the detection of disease recurrence were 94.5 %, 87.6 % and 89.6 % respectively. CONCLUSION FDG PET/CT is a suitable modality for early detection of asymptomatic recurrence of malignant melanoma. Asymptomatic recurrence most commonly occurs in lymph nodes. Sex, nodal metastasis and tumour pathologic features are predictors of recurrence.

68Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation Dosimetry, and First-in-Human PET/CT Imaging of Infections

Ubiquicidin is an antimicrobial peptide with great potential for nuclear imaging of infectious diseases, as its cationic-rich fragment TGRAKRRMQYNRR (UBI) has been functionalized with NOTA to allow complexation to 68Ga (68Ga-NOTA-UBI). We herein assess the cytotoxicity and radiation dosimetry for 68Ga-NOTA-UBI and a first-in-human evaluation to diagnose infectious processes. Methods: Cytotoxicity was evaluated in green monkey kidney epithelial (Vero) cells and MT-4 leukocytes. Tracer susceptibility was studied in vitro using different bacterial and fungal strains. PET/CT-based biodistribution, pharmacokinetics, and radiation dosimetry were performed on nonhuman primates. Two healthy volunteers and 3 patients with suspected infection underwent 68Ga-NOTA-UBI PET/CT imaging. Results: Negligible cytotoxicity was determined for NOTA-UBI. 68Ga-NOTA-UBI showed moderate blood clearance (29-min half-life) and predominant renal clearance in nonhuman primates. Human radiation dose estimates indicated the bladder wall as the dose-critical tissue (185 μSv/MBq), followed by the kidneys (23 μSv/MBq). The total absorbed body dose was low (<7 μSv/MBq); the effective dose was estimated at 17 μSv/MBq. 68Ga-NOTA-UBI could diagnose bone- and soft-tissue infection in 3 of 3 patients. Conclusion: 68Ga-NOTA-UBI is considered a nontoxic, safe-to-administer radiopharmaceutical unlikely to cause adverse effects in humans. The favorable tracer biodistribution and the first-in-human results will make 68Ga-NOTA-UBI PET/CT an encouraging future diagnostic technique with auxiliary clinical relevance.

68Ga-PSMA-HBED-CC PET/CT imaging in Black versus White South African patients with prostate carcinoma presenting with a low volume, androgen-dependent biochemical recurrence: a prospective study

Objective To compare the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA)-HBED-CC PET/computed tomography (CT) imaging for the detection of androgen-dependent recurrent prostate carcinoma (ADPC) in Black South Africans (BSAs) versus White South Africans (WSAs) with increasing serum prostate-specific antigen (PSA) values below or equal to 10 ng/ml. Patients and methods A total of 61 patients with ADPC were prospectively included in the study (mean age: 66.7 years): 38 WSAs and 23 BSAs. 68Ga-PSMA-HBED-CC PET/CT imaging results obtained were related to serum PSA levels and to ethnicity. Results A total of 41 (67%) patients had a positive 68Ga-PSMA-HBED-CC scan result. 68Ga-PSMA-HBED-CC PET/CT positivity was significantly higher in patients with PSA values more than 2 ng/ml [32/38 (84%) patients] when compared with patients with PSA values less than 0.5 ng/ml [6/11 (55%) patients] or PSA values of 0.5–2 ng/ml [3/12 (25%) patients] (P=0.0001). Mean PSA values proved not significantly different in patients presenting with extrapelvic involvement when compared with those with intrapelvic involvement or between patients who presented with bone involvement versus those who did not on 68Ga-PSMA-HBED-CC PET/CT) (P≥0.147). Age, Gleason-scores, median PSA values, the frequency of a positive scan result, the frequency of bone involvement, and extrapelvic involvement proved similar in WSAs and BSAs (P≥0.417). Conclusion 68Ga-PSMA-HBED-CC PET/CT imaging identified a recurrence in 67% of the patients under study. Higher PSA levels were associated with 68Ga-PSMA-HBED-CC PET/CT positivity and the detection rate. Imaging results obtained proved similar in BSAs and WSAs, suggesting that the tumor burden and growth rate of ADPC are similar in both races.

Higher preablative serum thyroid-stimulating hormone level predicts radioiodine ablation effectiveness in patients with differentiated thyroid carcinoma.

Introduction Radioiodine ablation of remnant thyroid tissue is an important adjuvant therapy of differentiated thyroid carcinoma (DTC) after thyroidectomy. Elevated serum thyroid-stimulating hormone (TSH) level is necessary for successful ablation. The optimum level of serum TSH level necessary for successful radioiodine ablation of well-DTC is, however, yet to be defined. We aimed to determine whether higher serum TSH level will result in a better rate of complete ablation of well-DTC using iodine-131 (131I) following initial thyroidectomy. Patients and methods A total of 109 patients with differentiated thyroid cancer were divided into four treatment groups on the basis of serum TSH levels. They were followed up from 6 to 12 months after treatment with stimulated serum thyroglobulin level and a diagnostic whole-body scan with radioactive iodine 131I to determine early response. Results Sixty-four patients had papillary thyroid carcinoma, whereas 45 patients had follicular carcinoma. An excellent response was observed in 66.7% of patients with TSH level more than 90 &mgr;IU/ml, 72.2% in the group with TSH level of 60–89 &mgr;IU/ml, 48.5% when TSH was 30–59 &mgr;IU/ml and 26.7% when TSH was less than 30 &mgr;IU/ml (P=0.002). Conclusion Higher preablative serum TSH predicts a better rate of ablation in patients with differentiated thyroid cancer treated with 131I after thyroidectomy.

68Ga-PSMA PET/CT Replacing Bone Scan in the Initial Staging of Skeletal Metastasis in Prostate Cancer: A Fait Accompli?

Micro‐Abstract We compared the findings of technetium‐99m–10‐metacyloyloxydecyl dihydrogen phosphate (99mTc‐MDP) bone scintigraphy and 68Ga–prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in 113 patients who underwent initial skeletal staging for prostate cancer. 68Ga‐PSMA PET/CT was found to be better than 99mTc‐MDP bone scintigraphy because of ability to additionally detect lytic and bone marrow lesions. 68Ga‐PSMA PET/CT could potentially replace bone scan for initial staging of skeletal metastases. Purpose 68 Ga ligands targeting prostate‐specific membrane antigen (PSMA) are rapidly emerging as a significant step forward in the management of prostate cancer. PSMA is a type II transmembrane protein with high expression in prostate carcinoma cells. We prospectively evaluated the use of 68Ga‐PSMA positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer and compared the results to those for technetium‐99m (99mTc)‐10‐metacyloyloxydecyl dihydrogen phosphate (MDP) bone scintigraphy (BS). Patients and Methods A total 113 patients with biopsy‐proven prostate cancer referred for standard‐of‐care BS were prospectively enrolled onto this study. 68Ga‐PSMA PET/CT was performed after BS. Metastasis diagnosed on each technique was compared against a final diagnosis based on CT, magnetic resonance imaging, skeletal survey, clinical follow‐up, and histologic correlation. Results Ninety‐one bone lesions were interpreted as bone metastases in 25 men undergoing 68Ga‐PSMA PET/CT compared to only 61 lesions in 19 men undergoing 99mTc‐MDP BS. Of the 7 bone scans that missed skeletal metastases, 54% of these missed lesions were due to either marrow or lytic skeletal metastases. The median standardized uptake value in all malignant bone lesions was 13.84. 68Ga‐PSMA PET/CT showed significantly higher sensitivity and accuracy than BS (96.2% vs. 73.1%, and 99.1% vs. 84.1%) for the detection of skeletal lesions. For extraskeletal lesions, 68Ga‐PSMA PET/CT showed an additional 96 unexpected lesions with a median standardized uptake value of 17.6. Conclusion 68 Ga‐PSMA PET/CT is superior to and can potentially replace bone scan in the evaluation for skeletal metastases in the clinical and trial setting because of its ability to detect lytic and bone marrow metastases.

Salivary Gland Activity Obscures Mandibular Metastasis of Prostate Carcinoma on 68Ga–Prostate-Specific Membrane Antigen PET

We report a case of a 65-year-old man with prostate cancer; his treatment history included radical prostatectomy followed by radiation therapy and subsequent androgen deprivation therapy for more than 5 years. He currently presented with a history of rising prostate-specific antigen and complained of jaw aches. Ga-prostate-specific membrane antigen PET/CT study performed for suspected biochemical recurrence demonstrated vertebral lesions and lesion in his jaw. Subsequent biopsy of jaw lesion demonstrated prostate cancer metastases.